To the question of the dualism of neutrophils' role in the processes of carcinogenesis, as well as the possibility of cell application for malignant neoplasm therapy

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

Neutrophils are phagocytic, myeloid-type leukocytes that are the most common myeloid cells in human blood, normally comprising 65 to 80% of all circulating leukocytes. Over the years of research into these cells, more and more evidence has emerged demonstrating the functional plasticity of neutrophils and their ambiguous role in tumor development. Similar to the M1/M2 classification of macrophages, the N1/N2 paradigm can be applied to neutrophils, where N1 neutrophils exhibit tumor-suppressive properties, while N2 neutrophils promote tumor development and suppression of immunity. An important natural feature of neutrophils is their mobility and ability to overcome physical barriers, which is why these cells, as well as their vesicles and membranes, can be used to deliver therapeutic drugs to tumor cells. Moreover, neutrophils themselves can be activated and mobilized to fight tumors. This review describes the current state of research into the role of neutrophils in carcinogenesis, as well as possible approaches to the use of these cells and their derivatives as delivery systems for therapeutic drugs for the treatment of malignant neoplasms.

Авторлар туралы

A. Gabashvili

Prokhorov General Physics Institute of the Russian Academy of Sciences; Koltzov Institute of Developmental Biology of the Russian Academy of Sciences

Email: anastasiacit@gmail.com
Ресей, 119991 Moscow; 119334 Moscow

A. Vasyukova

Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Health of the Russian Federation

Email: anastasiacit@gmail.com
Ресей, 119034 Moscow

A. Rakitina

Prokhorov General Physics Institute of the Russian Academy of Sciences; Moscow Institute of Physics and Technology

Email: anastasiacit@gmail.com
Ресей, 119991 Moscow; 141701 Dolgoprudny, Moscow Region

A. Garanina

National University of Science and Technology “MISIS”

Хат алмасуға жауапты Автор.
Email: anastasiacit@gmail.com
Ресей, 119049 Moscow

Әдебиет тізімі

  1. Ley, K., Hoffman, H. M., Kubes, P., Cassatella, M. A., Zychlinsky, A., Hedrick, C. C., and Catz, S. D. (2018) Neutrophils: new insights and open questions, Sci. Immunol., 3, doi: 10.1126/sciimmunol.aat4579.
  2. Petri, B., Phillipson, M., and Kubes, P. (2008) The physiology of leukocyte recruitment: an in vivo perspective, J. Immunol., 180, 6439-6446, doi: 10.4049/jimmunol.180.10.6439.
  3. Naumenko, V., Turk, M., Jenne, C. N., and Kim, S. J. (2018) Neutrophils in viral infection, Cell Tissue Res., 371, 505-516, doi: 10.1007/s00441-017-2763-0.
  4. Shaul, M. E., and Fridlender, Z. G. (2019) Tumour-associated neutrophils in patients with cancer, Nat. Rev. Clin. Oncol., 16, 601-620, doi: 10.1038/s41571-019-0222-4.
  5. Nishida, J., Momoi, Y., Miyakuni, K., Tamura, Y., Takahashi, K., Koinuma, D., Miyazono, K., and Ehata, S. (2020) Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis, Nat. Cell Biol., 22, 465-475, doi: 10.1038/s41556-020-0491-2.
  6. Faget, J., Groeneveld, S., Boivin, G., Sankar, M., Zangger, N., Garcia, M., Guex, N., Zlobec, I., Steiner, L., Piersigilli, A., Xenarios, I., and Meylan, E. (2017) Neutrophils and Snail orchestrate the establishment of a pro-tumor microenvironment in lung cancer, Cell Rep., 21, 3190-3204, doi: 10.1016/j.celrep.2017.11.052.
  7. Wang, Q., Hu, B., Hu, X., Kim, H., Squatrito, M., Scarpace, L., deCarvalho, A. C., Lyu, S., Li, P., Li, Y., Barthel, F., Cho, H. J., Lin, Y. H., Satani, N., Martinez-Ledesma, E., Zheng, S., Chang, E., Gabriel Sauve, C. E., Olar, A., Lan, Z. D., et al. (2018) Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment, Cancer Cell, 33, 152, doi: 10.1016/j.ccell.2017.12.012.
  8. Kruger, P., Saffarzadeh, M., Weber, A. N., Rieber, N., Radsak, M., von Bernuth, H., Benarafa, C., Roos, D., Skokowa, J., and Hartl, D. (2015) Neutrophils: between host defence, immune modulation, and tissue injury, PLoS Pathog., 11, e1004651, doi: 10.1371/journal.ppat.1004651.
  9. Chu, D., Dong, X., Zhao, Q., Gu, J., and Wang, Z. (2017) Photosensitization priming of tumor microenvironments improves delivery of nanotherapeutics via neutrophil infiltration, Adv. Mater., 29, doi: 10.1002/adma.201701021.
  10. Shi, Y., van der Meel, R., Chen, X., and Lammers, T. (2020) The EPR effect and beyond: Strategies to improve tumor targeting and cancer nanomedicine treatment efficacy, Theranostics, 10, 7921-7924, doi: 10.7150/thno.49577.
  11. Zhao, Q., Jiang, D., Sun, X., Mo, Q., Chen, S., Chen, W., Gui, R., and Ma, X. (2021) Biomimetic nanotherapy: core-shell structured nanocomplexes based on the neutrophil membrane for targeted therapy of lymphoma, J. Nanobiotechnol., 19, 179, doi: 10.1186/s12951-021-00922-4.
  12. Kang, T., Zhu, Q., Wei, D., Feng, J., Yao, J., Jiang, T., Song, Q., Wei, X., Chen, H., Gao, X., and Chen, J. (2017) Nanoparticles coated with neutrophil membranes can effectively treat cancer metastasis, ACS Nano, 11, 1397-1411, doi: 10.1021/acsnano.6b06477.
  13. Wang, J., Tang, W., Yang, M., Yin, Y., Li, H., Hu, F., Tang, L., Ma, X., Zhang, Y., and Wang, Y. (2021) Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy, Biomaterials, 273, 120784, doi: 10.1016/j.biomaterials.2021.120784.
  14. Hacbarth, E., and Kajdacsy-Balla, A. (1986) Low density neutrophils in patients with systemic lupus erythematosus, rheumatoid arthritis, and acute rheumatic fever, Arthritis Rheum., 29, 1334-1342, doi: 10.1002/art.1780291105.
  15. Liu, Y., Hu, Y., Gu, F., Liang, J., Zeng, Y., Hong, X., Zhang, K., and Liu, L. (2017) Phenotypic and clinical characterization of low density neutrophils in patients with advanced lung adenocarcinoma, Oncotarget, 8, 90969-90978, doi: 10.18632/oncotarget.18771.
  16. Ui Mhaonaigh, A., Coughlan, A. M., Dwivedi, A., Hartnett, J., Cabral, J., Moran, B., Brennan, K., Doyle, S. L., Hughes, K., Lucey, R., Floudas, A., Fearon, U., McGrath, S., Cormican, S., De Bhailis, A., Molloy, E. J., Brady, G., and Little, M. A. (2019) Low density granulocytes in ANCA vasculitis are heterogenous and hypo-responsive to anti-myeloperoxidase antibodies, Front. Immunol., 10, 2603, doi: 10.3389/fimmu.2019.02603.
  17. Deng, Y., Ye, J., Luo, Q., Huang, Z., Peng, Y., Xiong, G., Guo, Y., Jiang, H., and Li, J. (2016) Low-density granulocytes are elevated in mycobacterial infection and associated with the severity of tuberculosis, PLoS One, 11, e0153567, doi: 10.1371/journal.pone.0153567.
  18. Ssemaganda, A., Kindinger, L., Bergin, P., Nielsen, L., Mpendo, J., Ssetaala, A., Kiwanuka, N., Munder, M., Teoh, T. G., Kropf, P., and Muller, I. (2014) Characterization of neutrophil subsets in healthy human pregnancies, PLoS One, 9, e85696, doi: 10.1371/journal.pone.0085696.
  19. Giallongo, C., Tibullo, D., Parrinello, N. L., La Cava, P., Di Rosa, M., Bramanti, V., Di Raimondo, C., Conticello, C., Chiarenza, A., Palumbo, G. A., Avola, R., Romano, A., and Di Raimondo, F. (2016) Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC), Oncotarget, 7, 85764-85775, doi: 10.18632/oncotarget.7969.
  20. Zhou, J., Nefedova, Y., Lei, A., and Gabrilovich, D. (2018) Neutrophils and PMN-MDSC: Their biological role and interaction with stromal cells, Semin. Immunol., 35, 19-28, doi: 10.1016/j.smim.2017.12.004.
  21. Sagiv, J. Y., Michaeli, J., Assi, S., Mishalian, I., Kisos, H., Levy, L., Damti, P., Lumbroso, D., Polyansky, L., Sionov, R. V., Ariel, A., Hovav, A. H., Henke, E., Fridlender, Z. G., and Granot, Z. (2015) Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer, Cell Rep., 10, 562-573, doi: 10.1016/j.celrep.2014.12.039.
  22. Bejarano, L., Jordao, M. J. C., and Joyce, J. A. (2021) Therapeutic targeting of the tumor microenvironment, Cancer Discov., 11, 933-959, doi: 10.1158/2159-8290.CD-20-1808.
  23. McKenna, E., Mhaonaigh, A. U., Wubben, R., Dwivedi, A., Hurley, T., Kelly, L. A., Stevenson, N. J., Little, M. A., and Molloy, E. J. (2021) Neutrophils: Need for Standardized Nomenclature, Front. Immunol., 12, 602963, doi: 10.3389/fimmu.2021.602963.
  24. Ng, L. G., Ostuni, R., and Hidalgo, A. (2019) Heterogeneity of neutrophils, Nat. Rev. Immunol., 19, 255-265, doi: 10.1038/s41577-019-0141-8.
  25. Liew, P. X., and Kubes, P. (2019) The neutrophil’s role during health and disease, Physiol. Rev., 99, 1223-1248, doi: 10.1152/physrev.00012.2018.
  26. Lieschke, G. J., Grail, D., Hodgson, G., Metcalf, D., Stanley, E., Cheers, C., Fowler, K. J., Basu, S., Zhan, Y. F., and Dunn, A. R. (1994) Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization, Blood, 84, 1737-1746.
  27. Liu, F., Wu, H. Y., Wesselschmidt, R., Kornaga, T., and Link, D. C. (1996) Impaired production and increased apoptosis of neutrophils in granulocyte colony-stimulating factor receptor-deficient mice, Immunity, 5, 491-501, doi: 10.1016/s1074-7613(00)80504-x.
  28. Eash, K. J., Greenbaum, A. M., Gopalan, P. K., and Link, D. C. (2010) CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow, J. Clin. Invest., 120, 2423-2431, doi: 10.1172/JCI41649.
  29. Casanova-Acebes, M., Pitaval, C., Weiss, L. A., Nombela-Arrieta, C., Chevre, R., A-González, N., Kunisaki, Y., Zhang, D., van Rooijen, N., Silberstein, L. E., Weber, C., Nagasawa, T., Frenette, P. S., Castrillo, A., and Hidalgo, A. (2013) Rhythmic modulation of the hematopoietic niche through neutrophil clearance, Cell, 153, 1025-1035, doi: 10.1016/j.cell.2013.04.040.
  30. Zhang, D., Chen, G., Manwani, D., Mortha, A., Xu, C., Faith, J. J., Burk, R. D., Kunisaki, Y., Jang, J. E., Scheiermann, C., Merad, M., and Frenette, P. S. (2015) Neutrophil ageing is regulated by the microbiome, Nature, 525, 528-532, doi: 10.1038/nature15367.
  31. Adrover, J. M., Del Fresno, C., Crainiciuc, G., Cuartero, M. I., Casanova-Acebes, M., Weiss, L. A., Huerga-Encabo, H., Silvestre-Roig, C., Rossaint, J., Cossio, I., Lechuga-Vieco, A. V., Garcia-Prieto, J., Gomez-Parrizas, M., Quintana, J. A., Ballesteros, I., Martin-Salamanca, S., Aroca-Crevillen, A., Chong, S. Z., Evrard, M., Balabanian, K., et al. (2019) A neutrophil timer coordinates immune defense and vascular protection, Immunity, 51, 966-967, doi: 10.1016/j.immuni.2019.11.001.
  32. Lakschevitz, F. S., Visser, M. B., Sun, C., and Glogauer, M. (2015) Neutrophil transcriptional profile changes during transit from bone marrow to sites of inflammation, Cell Mol. Immunol., 12, 53-65, doi: 10.1038/cmi.2014.37.
  33. Puga, I., Cols, M., Barra, C. M., He, B., Cassis, L., Gentile, M., Comerma, L., Chorny, A., Shan, M., Xu, W., Magri, G., Knowles, D. M., Tam, W., Chiu, A., Bussel, J. B., Serrano, S., Lorente, J. A., Bellosillo, B., Lloreta, J., Juanpere, N., et al. (2011) B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen, Nat. Immunol., 13, 170-180, doi: 10.1038/ni.2194.
  34. Casanova-Acebes, M., Nicolas-Avila, J. A., Li, J. L., Garcia-Silva, S., Balachander, A., Rubio-Ponce, A., Weiss, L. A., Adrover, J. M., Burrows, K., A-González, N., Ballesteros, I., Devi, S., Quintana, J. A., Crainiciuc, G., Leiva, M., Gunzer, M., Weber, C., Nagasawa, T., Soehnlein, O., Merad, M., et al. (2018) Neutrophils instruct homeostatic and pathological states in naive tissues, J. Exp. Med., 215, 2778-2795, doi: 10.1084/jem.20181468.
  35. Mantovani, A., Cassatella, M. A., Costantini, C., and Jaillon, S. (2011) Neutrophils in the activation and regulation of innate and adaptive immunity, Nat. Rev. Immunol., 11, 519-531, doi: 10.1038/nri3024.
  36. Lok, L. S. C., Dennison, T. W., Mahbubani, K. M., Saeb-Parsy, K., Chilvers, E. R., and Clatworthy, M. R. (2019) Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes, Proc. Natl. Acad. Sci. USA, 116, 19083-19089, doi: 10.1073/pnas.1905054116.
  37. Vogt, K. L., Summers, C., Chilvers, E. R., and Condliffe, A. M. (2018) Priming and de-priming of neutrophil responses in vitro and in vivo, Eur. J. Clin. Invest., 48 Suppl 2, e12967, doi: 10.1111/eci.12967.
  38. Mora-Jensen, H., Jendholm, J., Fossum, A., Porse, B., Borregaard, N., and Theilgaard-Monch, K. (2011) Technical advance: immunophenotypical characterization of human neutrophil differentiation, J. Leukoc. Biol., 90, 629-634, doi: 10.1189/jlb.0311123.
  39. Lominadze, G., Powell, D. W., Luerman, G. C., Link, A. J., Ward, R. A., and McLeish, K. R. (2005) Proteomic analysis of human neutrophil granules, Mol. Cell Proteomics, 4, 1503-1521, doi: 10.1074/mcp.M500143-MCP200.
  40. Rorvig, S., Ostergaard, O., Heegaard, N. H., and Borregaard, N. (2013) Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors, J. Leukoc. Bio., 94, 711-721, doi: 10.1189/jlb.1212619.
  41. Yin, C., and Heit, B. (2018) Armed for destruction: formation, function and trafficking of neutrophil granules, Cell Tissue Res., 371, 455-471, doi: 10.1007/s00441-017-2731-8.
  42. Uriarte, S. M., Powell, D. W., Luerman, G. C., Merchant, M. L., Cummins, T. D., Jog, N. R., Ward, R. A., and McLeish, K. R. (2008) Comparison of proteins expressed on secretory vesicle membranes and plasma membranes of human neutrophils, J. Immunol., 180, 5575-5581, doi: 10.4049/jimmunol.180.8.5575.
  43. Jethwaney, D., Islam, M. R., Leidal, K. G., de Bernabe, D. B., Campbell, K. P., Nauseef, W. M., and Gibson, B. W. (2007) Proteomic analysis of plasma membrane and secretory vesicles from human neutrophils, Proteome Sci., 5, 12, doi: 10.1186/1477-5956-5-12.
  44. Mahiddine, K., Blaisdell, A., Ma, S., Crequer-Grandhomme, A., Lowell, C. A., and Erlebacher, A. (2020) Relief of tumor hypoxia unleashes the tumoricidal potential of neutrophils, J. Clin. Invest., 130, 389-403, doi: 10.1172/JCI130952.
  45. Blaisdell, A., Crequer, A., Columbus, D., Daikoku, T., Mittal, K., Dey, S. K., and Erlebacher, A. (2015) Neutrophils oppose uterine epithelial carcinogenesis via debridement of hypoxic tumor cells, Cancer Cell, 28, 785-799, doi: 10.1016/j.ccell.2015.11.005.
  46. Finisguerra, V., Di Conza, G., Di Matteo, M., Serneels, J., Costa, S., Thompson, A. A., Wauters, E., Walmsley, S., Prenen, H., Granot, Z., Casazza, A., and Mazzone, M. (2015) MET is required for the recruitment of anti-tumoural neutrophils, Nature, 522, 349-353, doi: 10.1038/nature14407.
  47. Koga, Y., Matsuzaki, A., Suminoe, A., Hattori, H., and Hara, T. (2004) Neutrophil-derived TNF-related apoptosis-inducing ligand (TRAIL): a novel mechanism of antitumor effect by neutrophils, Cancer Res., 64, 1037-1043, doi: 10.1158/0008-5472.can-03-1808.
  48. Hagerling, C., Gonzalez, H., Salari, K., Wang, C. Y., Lin, C., Robles, I., van Gogh, M., Dejmek, A., Jirstrom, K., and Werb, Z. (2019) Immune effector monocyte-neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer, Proc. Natl. Acad. Sci. USA, 116, 21704-21714, doi: 10.1073/pnas.1907660116.
  49. Massara, M., Bonavita, O., Savino, B., Caronni, N., Mollica Poeta, V., Sironi, M., Setten, E., Recordati, C., Crisafulli, L., Ficara, F., Mantovani, A., Locati, M., and Bonecchi, R. (2018) ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity, Nat. Commun., 9, 676, doi: 10.1038/s41467-018-03080-8.
  50. Granot, Z., Henke, E., Comen, E. A., King, T. A., Norton, L., and Benezra, R. (2011) Tumor entrained neutrophils inhibit seeding in the premetastatic lung, Cancer Cell, 20, 300-314, doi: 10.1016/j.ccr.2011.08.012.
  51. Singhal, S., Bhojnagarwala, P. S., O'Brien, S., Moon, E. K., Garfall, A. L., Rao, A. S., Quatromoni, J. G., Stephen, T. L., Litzky, L., Deshpande, C., Feldman, M. D., Hancock, W. W., Conejo-Garcia, J. R., Albelda, S. M., and Eruslanov, E. B. (2016) Origin and role of a subset of tumor-associated neutrophils with antigen-presenting cell features in early-stage human lung cancer, Cancer Cell, 30, 120-135, doi: 10.1016/j.ccell.2016.06.001.
  52. Eruslanov, E. B., Bhojnagarwala, P. S., Quatromoni, J. G., Stephen, T. L., Ranganathan, A., Deshpande, C., Akimova, T., Vachani, A., Litzky, L., Hancock, W. W., Conejo-Garcia, J. R., Feldman, M., Albelda, S. M., and Singhal, S. (2014) Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer, J. Clin. Invest., 124, 5466-5480, doi: 10.1172/JCI77053.
  53. Ponzetta, A., Carriero, R., Carnevale, S., Barbagallo, M., Molgora, M., Perucchini, C., Magrini, E., Gianni, F., Kunderfranco, P., Polentarutti, N., Pasqualini, F., Di Marco, S., Supino, D., Peano, C., Cananzi, F., Colombo, P., Pilotti, S., Alomar, S. Y., Bonavita, E., Galdiero, M. R., et al. (2019) Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors, Cell, 178, 346-360, e324, doi: 10.1016/j.cell.2019.05.047.
  54. Grivennikov, S. I., Wang, K., Mucida, D., Stewart, C. A., Schnabl, B., Jauch, D., Taniguchi, K., Yu, G. Y., Osterreicher, C. H., Hung, K. E., Datz, C., Feng, Y., Fearon, E. R., Oukka, M., Tessarollo, L., Coppola, V., Yarovinsky, F., Cheroutre, H., Eckmann, L., Trinchieri, G., et al. (2012) Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth, Nature, 491, 254-258, doi: 10.1038/nature11465.
  55. Brennan, C. A., and Garrett, W. S. (2016) Gut microbiota, inflammation, and colorectal cancer, Annu. Rev. Microbiol., 70, 395-411, doi: 10.1146/annurev-micro-102215-095513.
  56. Triner, D., Devenport, S. N., Ramakrishnan, S. K., Ma, X., Frieler, R. A., Greenson, J. K., Inohara, N., Nunez, G., Colacino, J. A., Mortensen, R. M., and Shah, Y. M. (2019) Neutrophils restrict tumor-associated microbiota to reduce growth and invasion of colon tumors in mice, Gastroenterology, 156, 1467-1482, doi: 10.1053/j.gastro.2018.12.003.
  57. Jin, C., Lagoudas, G. K., Zhao, C., Bullman, S., Bhutkar, A., Hu, B., Ameh, S., Sandel, D., Liang, X. S., Mazzilli, S., Whary, M. T., Meyerson, M., Germain, R., Blainey, P. C., Fox, J. G., and Jacks, T. (2019) Commensal microbiota promote lung cancer development via gammadelta T cells, Cell, 176, 998-1013, e1016, doi: 10.1016/j.cell.2018.12.040.
  58. Hao, Y., Baker, D., and Ten Dijke, P. (2019) TGF-beta-mediated epithelial-mesenchymal transition and cancer metastasis, Int. J. Mol. Sci., 20, doi: 10.3390/ijms20112767.
  59. Li, Z., Pang, Y., Gara, S. K., Achyut, B. R., Heger, C., Goldsmith, P. K., Lonning, S., and Yang, L. (2012) Gr-1+CD11b+ cells are responsible for tumor promoting effect of TGF-beta in breast cancer progression, Int. J. Cancer, 131, 2584-2595, doi: 10.1002/ijc.27572.
  60. Waight, J. D., Netherby, C., Hensen, M. L., Miller, A., Hu, Q., Liu, S., Bogner, P. N., Farren, M. R., Lee, K. P., Liu, K., and Abrams, S. I. (2013) Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis, J. Clin. Invest., 123, 4464-4478, doi: 10.1172/JCI68189.
  61. Fridlender, Z. G., Sun, J., Kim, S., Kapoor, V., Cheng, G., Ling, L., Worthen, G. S., and Albelda, S. M. (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN, Cancer Cell, 16, 183-194, doi: 10.1016/j.ccr.2009.06.017.
  62. Youn, J. I., Kumar, V., Collazo, M., Nefedova, Y., Condamine, T., Cheng, P., Villagra, A., Antonia, S., McCaffrey, J. C., Fishman, M., Sarnaik, A., Horna, P., Sotomayor, E., and Gabrilovich, D. I. (2013) Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer, Nat. Immunol., 14, 211-220, doi: 10.1038/ni.2526.
  63. Casbon, A. J., Reynaud, D., Park, C., Khuc, E., Gan, D. D., Schepers, K., Passegue, E., and Werb, Z. (2015) Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils, Proc. Natl. Acad. Sci. USA, 112, E566-575, doi: 10.1073/pnas.1424927112.
  64. Jablonska, J., Leschner, S., Westphal, K., Lienenklaus, S., and Weiss, S. (2010) Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model, J. Clin. Invest., 120, 1151-1164, doi: 10.1172/JCI37223.
  65. Wu, C. F., Andzinski, L., Kasnitz, N., Kroger, A., Klawonn, F., Lienenklaus, S., Weiss, S., and Jablonska, J. (2015) The lack of type I interferon induces neutrophil-mediated pre-metastatic niche formation in the mouse lung, Int. J. Cancer, 137, 837-847, doi: 10.1002/ijc.29444.
  66. Mishalian, I., Bayuh, R., Levy, L., Zolotarov, L., Michaeli, J., and Fridlender, Z. G. (2013) Tumor-associated neutrophils (TAN) develop pro-tumorigenic properties during tumor progression, Cancer Immunol. Immunother., 62, 1745-1756, doi: 10.1007/s00262-013-1476-9.
  67. Novitskiy, S. V., Pickup, M. W., Chytil, A., Polosukhina, D., Owens, P., and Moses, H. L. (2012) Deletion of TGF-beta signaling in myeloid cells enhances their anti-tumorigenic properties, J. Leukoc. Biol., 92, 641-651, doi: 10.1189/jlb.1211639.
  68. Shaul, M. E., Levy, L., Sun, J., Mishalian, I., Singhal, S., Kapoor, V., Horng, W., Fridlender, G., Albelda, S. M., and Fridlender, Z. G. (2016) Tumor-associated neutrophils display a distinct N1 profile following TGFβ modulation: A transcriptomics analysis of pro- vs. antitumor TANs, Oncoimmunology, 5, e1232221, doi: 10.1080/2162402X.2016.1232221.
  69. Andzinski, L., Kasnitz, N., Stahnke, S., Wu, C. F., Gereke, M., von Kockritz-Blickwede, M., Schilling, B., Brandau, S., Weiss, S., and Jablonska, J. (2016) Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human, Int. J. Cancer, 138, 1982-1993, doi: 10.1002/ijc.29945.
  70. Glodde, N., Bald, T., van den Boorn-Konijnenberg, D., Nakamura, K., O'Donnell, J. S., Szczepanski, S., Brandes, M., Eickhoff, S., Das, I., Shridhar, N., Hinze, D., Rogava, M., van der Sluis, T. C., Ruotsalainen, J. J., Gaffal, E., Landsberg, J., Ludwig, K. U., Wilhelm, C., Riek-Burchardt, M., Muller, A. J., et al. (2017) Reactive neutrophil responses dependent on the receptor tyrosine kinase c-MET limit cancer immunotherapy, Immunity, 47, 789-802.e789, doi: 10.1016/j.immuni.2017.09.012.
  71. Nielsen, S. R., Strobech, J. E., Horton, E. R., Jackstadt, R., Laitala, A., Bravo, M. C., Maltese, G., Jensen, A. R. D., Reuten, R., Rafaeva, M., Karim, S. A., Hwang, C. I., Arnes, L., Tuveson, D. A., Sansom, O. J., Morton, J. P., and Erler, J. T. (2021) Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade, Nat. Commun., 12, 3414, doi: 10.1038/s41467-021-23731-7.
  72. Nadkarni, S., Dalli, J., Hollywood, J., Mason, J. C., Dasgupta, B., and Perretti, M. (2014) Investigational analysis reveals a potential role for neutrophils in giant-cell arteritis disease progression, Circ. Res., 114, 242-248, doi: 10.1161/CIRCRESAHA.114.301374.
  73. Tyagi, A., Sharma, S., Wu, K., Wu, S. Y., Xing, F., Liu, Y., Zhao, D., Deshpande, R. P., D'Agostino, R. B., Jr., and Watabe, K. (2021) Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung, Nat. Commun., 12, 474, doi: 10.1038/s41467-020-20733-9.
  74. Chen, Q., Yin, H., Liu, S., Shoucair, S., Ding, N., Ji, Y., Zhang, J., Wang, D., Kuang, T., Xu, X., Yu, J., Wu, W., Pu, N., and Lou, W. (2022) Prognostic value of tumor-associated N1/N2 neutrophil plasticity in patients following radical resection of pancreas ductal adenocarcinoma, J. Immunother. Cancer, 10, doi: 10.1136/jitc-2022-005798.
  75. Antuamwine, B. B., Bosnjakovic, R., Hofmann-Vega, F., Wang, X., Theodosiou, T., Iliopoulos, I., and Brandau, S. (2023) N1 versus N2 and PMN-MDSC: A critical appraisal of current concepts on tumor-associated neutrophils and new directions for human oncology, Immunol. Rev., 314, 250-279, doi: 10.1111/imr.13176.
  76. Schernberg, A., Blanchard, P., Chargari, C., and Deutsch, E. (2017) Neutrophils, a candidate biomarker and target for radiation therapy? Acta Oncol., 56, 1522-1530, doi: 10.1080/0284186X.2017.1348623.
  77. Chung, A. S., Wu, X., Zhuang, G., Ngu, H., Kasman, I., Zhang, J., Vernes, J. M., Jiang, Z., Meng, Y. G., Peale, F. V., Ouyang, W., and Ferrara, N. (2013) An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy, Nat. Med., 19, 1114-1123, doi: 10.1038/nm.3291.
  78. Schiffmann, L. M., Fritsch, M., Gebauer, F., Gunther, S. D., Stair, N. R., Seeger, J. M., Thangarajah, F., Dieplinger, G., Bludau, M., Alakus, H., Gobel, H., Quaas, A., Zander, T., Hilberg, F., Bruns, C. J., Kashkar, H., and Coutelle, O. (2019) Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer, Br. J. Cancer, 120, 69-78, doi: 10.1038/s41416-018-0198-3.
  79. Hu, N., Westra, J., Rutgers, A., Doornbos-Van der Meer, B., Huitema, M. G., Stegeman, C. A., Abdulahad, W. H., Satchell, S. C., Mathieson, P. W., Heeringa, P., and Kallenberg, C. G. (2011) Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration, Arthritis Res. Ther., 13, R201, doi: 10.1186/ar3534.
  80. Jamieson, T., Clarke, M., Steele, C. W., Samuel, M. S., Neumann, J., Jung, A., Huels, D., Olson, M. F., Das, S., Nibbs, R. J., and Sansom, O. J. (2012) Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis, J. Clin. Invest., 122, 3127-3144, doi: 10.1172/JCI61067.
  81. Viola, A., Sarukhan, A., Bronte, V., and Molon, B. (2012) The pros and cons of chemokines in tumor immunology, Trends Immunol., 33, 496-504, doi: 10.1016/j.it.2012.05.007.
  82. Raccosta, L., Fontana, R., Maggioni, D., Lanterna, C., Villablanca, E. J., Paniccia, A., Musumeci, A., Chiricozzi, E., Trincavelli, M. L., Daniele, S., Martini, C., Gustafsson, J. A., Doglioni, C., Feo, S. G., Leiva, A., Ciampa, M. G., Mauri, L., Sensi, C., Prinetti, A., Eberini, I., et al. (2013) The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils, J. Exp. Med., 210, 1711-1728, doi: 10.1084/jem.20130440.
  83. Tazzyman, S., Lewis, C. E., and Murdoch, C. (2009) Neutrophils: key mediators of tumour angiogenesis, Int. J. Exp. Pathol., 90, 222-231, doi: 10.1111/j.1365-2613.2009.00641.x.
  84. Antonio, N., Bonnelykke-Behrndtz, M. L., Ward, L. C., Collin, J., Christensen, I. J., Steiniche, T., Schmidt, H., Feng, Y., and Martin, P. (2015) The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer, EMBO J., 34, 2219-2236, doi: 10.15252/embj.201490147.
  85. Zha, C., Meng, X., Li, L., Mi, S., Qian, D., Li, Z., Wu, P., Hu, S., Zhao, S., Cai, J., and Liu, Y. (2020) Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis, Cancer Biol. Med., 17, 154-168, doi: 10.20892/j.issn.2095-3941.2019.0353.
  86. Lerman, I., Ma, X., Seger, C., Maolake, A., Garcia-Hernandez, M. L., Rangel-Moreno, J., Ackerman, J., Nastiuk, K. L., Susiarjo, M., and Hammes, S. R. (2019) Epigenetic suppression of SERPINB1 promotes inflammation-mediated prostate cancer progression, Mol. Cancer Res., 17, 845-859, doi: 10.1158/1541-7786.MCR-18-0638.
  87. Ostafin, M., Ciepiela, O., Pruchniak, M., Wachowska, M., Ulinska, E., Mrowka, P., Glodkowska-Mrowka, E., and Demkow, U. (2021) Dynamic changes in the ability to release neutrophil extracellular traps in the course of childhood acute leukemias, Int. J. Mol. Sci., 22, doi: 10.3390/ijms22020821.
  88. Zhou, S. L., Zhou, Z. J., Hu, Z. Q., Huang, X. W., Wang, Z., Chen, E. B., Fan, J., Cao, Y., Dai, Z., and Zhou, J. (2016) Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib, Gastroenterology, 150, 1646-1658, e1617, doi: 10.1053/j.gastro.2016.02.040.
  89. Spiegel, A., Brooks, M. W., Houshyar, S., Reinhardt, F., Ardolino, M., Fessler, E., Chen, M. B., Krall, J. A., DeCock, J., Zervantonakis, I. K., Iannello, A., Iwamoto, Y., Cortez-Retamozo, V., Kamm, R. D., Pittet, M. J., Raulet, D. H., and Weinberg, R. A. (2016) Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells, Cancer Discov., 6, 630-649, doi: 10.1158/2159-8290.CD-15-1157.
  90. Wang, Z., Yang, C., Li, L., Jin, X., Zhang, Z., Zheng, H., Pan, J., Shi, L., Jiang, Z., Su, K., Li, B., Shao, X., Qiu, F., Yan, J., and Huang, J. (2020) Tumor-derived HMGB1 induces CD62L(dim) neutrophil polarization and promotes lung metastasis in triple-negative breast cancer, Oncogenesis, 9, 82, doi: 10.1038/s41389-020-00267-x.
  91. Bald, T., Quast, T., Landsberg, J., Rogava, M., Glodde, N., Lopez-Ramos, D., Kohlmeyer, J., Riesenberg, S., van den Boorn-Konijnenberg, D., Homig-Holzel, C., Reuten, R., Schadow, B., Weighardt, H., Wenzel, D., Helfrich, I., Schadendorf, D., Bloch, W., Bianchi, M. E., Lugassy, C., Barnhill, R. L., et al. (2014) Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma, Nature, 507, 109-113, doi: 10.1038/nature13111.
  92. Zhang, X., Shi, H., Yuan, X., Jiang, P., Qian, H., and Xu, W. (2018) Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration, Mol. Cancer, 17, 146, doi: 10.1186/s12943-018-0898-6.
  93. Szczerba, B. M., Castro-Giner, F., Vetter, M., Krol, I., Gkountela, S., Landin, J., Scheidmann, M. C., Donato, C., Scherrer, R., Singer, J., Beisel, C., Kurzeder, C., Heinzelmann-Schwarz, V., Rochlitz, C., Weber, W. P., Beerenwinkel, N., and Aceto, N. (2019) Neutrophils escort circulating tumour cells to enable cell cycle progression, Nature, 566, 553-557, doi: 10.1038/s41586-019-0915-y.
  94. Morimoto-Kamata, R., and Yui, S. (2017) Insulin-like growth factor-1 signaling is responsible for cathepsin G-induced aggregation of breast cancer MCF-7 cells, Cancer Sci., 108, 1574-1583, doi: 10.1111/cas.13286.
  95. Saini, M., Szczerba, B. M., and Aceto, N. (2019) Circulating tumor cell-neutrophil tango along the metastatic process, Cancer Res., 79, 6067-6073, doi: 10.1158/0008-5472.CAN-19-1972.
  96. Albrengues, J., Shields, M. A., Ng, D., Park, C. G., Ambrico, A., Poindexter, M. E., Upadhyay, P., Uyeminami, D. L., Pommier, A., Kuttner, V., Bruzas, E., Maiorino, L., Bautista, C., Carmona, E. M., Gimotty, P. A., Fearon, D. T., Chang, K., Lyons, S. K., Pinkerton, K. E., Trotman, L. C., et al. (2018) Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice, Science, 361, doi: 10.1126/science.aao4227.
  97. Liu, Y., Gu, Y., Han, Y., Zhang, Q., Jiang, Z., Zhang, X., Huang, B., Xu, X., Zheng, J., and Cao, X. (2016) Tumor exosomal RNAs promote lung pre-metastatic niche formation by activating alveolar epithelial TLR3 to recruit neutrophils, Cancer Cell, 30, 243-256, doi: 10.1016/j.ccell.2016.06.021.
  98. Lee, W., Ko, S. Y., Mohamed, M. S., Kenny, H. A., Lengyel, E., and Naora, H. (2019) Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum, J. Exp. Med., 216, 176-194, doi: 10.1084/jem.20181170.
  99. Carus, A., Ladekarl, M., Hager, H., Nedergaard, B. S., and Donskov, F. (2013) Tumour-associated CD66b+ neutrophil count is an independent prognostic factor for recurrence in localised cervical cancer, Br. J. Cancer, 108, 2116-2122, doi: 10.1038/bjc.2013.167.
  100. Watanabe, A., Harimoto, N., Araki, K., Kubo, N., Igarashi, T., Tsukagoshi, M., Ishii, N., Yamanaka, T., Yoshizumi, T., and Shirabe, K. (2019) Absolute neutrophil count predicts postoperative prognosis in mass-forming intrahepatic cholangiocarcinoma, Anticancer Res., 39, 941-947, doi: 10.21873/anticanres.13197.
  101. Perego, M., Tyurin, V. A., Tyurina, Y. Y., Yellets, J., Nacarelli, T., Lin, C., Nefedova, Y., Kossenkov, A., Liu, Q., Sreedhar, S., Pass, H., Roth, J., Vogl, T., Feldser, D., Zhang, R., Kagan, V. E., and Gabrilovich, D. I. (2020) Reactivation of dormant tumor cells by modified lipids derived from stress-activated neutrophils, Sci. Transl. Med., 12, doi: 10.1126/scitranslmed.abb5817.
  102. Chung, J. Y., Tang, P. C., Chan, M. K., Xue, V. W., Huang, X. R., Ng, C. S., Zhang, D., Leung, K. T., Wong, C. K., Lee, T. L., Lam, E. W., Nikolic-Paterson, D. J., To, K. F., Lan, H. Y., and Tang, P. M. (2023) Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma, Nat. Commun., 14, 1794, doi: 10.1038/s41467-023-37515-8.
  103. Pylaeva, E., Harati, M. D., Spyra, I., Bordbari, S., Strachan, S., Thakur, B. K., Hoing, B., Franklin, C., Skokowa, J., Welte, K., Schadendorf, D., Bankfalvi, A., Brandau, S., Lang, S., and Jablonska, J. (2019) NAMPT signaling is critical for the proangiogenic activity of tumor-associated neutrophils, Int. J. Cancer, 144, 136-149, doi: 10.1002/ijc.31808.
  104. Zhang, Y., Diao, N., Lee, C. K., Chu, H. W., Bai, L., and Li, L. (2020) Neutrophils deficient in innate suppressor IRAK-M enhances anti-tumor immune responses, Mol. Ther., 28, 89-99, doi: 10.1016/j.ymthe.2019.09.019.
  105. Wisdom, A. J., Hong, C. S., Lin, A. J., Xiang, Y., Cooper, D. E., Zhang, J., Xu, E. S., Kuo, H. C., Mowery, Y. M., Carpenter, D. J., Kadakia, K. T., Himes, J. E., Luo, L., Ma, Y., Williams, N., Cardona, D. M., Haldar, M., Diao, Y., Markovina, S., Schwarz, J. K., et al. (2019) Neutrophils promote tumor resistance to radiation therapy, Proc. Natl. Acad. Sci. USA, 116, 18584-18589, doi: 10.1073/pnas.1901562116.
  106. Linde, I. L., Prestwood, T. R., Qiu, J., Pilarowski, G., Linde, M. H., Zhang, X., Shen, L., Reticker-Flynn, N. E., Chiu, D. K., Sheu, L. Y., Van Deursen, S., Tolentino, L. L., Song, W. C., and Engleman, E. G. (2023) Neutrophil-activating therapy for the treatment of cancer, Cancer Cell, 41, 356-372.e310, doi: 10.1016/j.ccell.2023.01.002.
  107. Timin, A. S., Litvak, M. M., Gorin, D. A., Atochina-Vasserman, E. N., Atochin, D. N., and Sukhorukov, G. B. (2018) Cell-based drug delivery and use of nano-and microcarriers for cell functionalization, Adv. Healthc. Mater., 7, doi: 10.1002/adhm.201700818.
  108. Margraf, A., Ley, K., and Zarbock, A. (2019) Neutrophil recruitment: from model systems to tissue-specific patterns, Trends Immunol., 40, 613-634, doi: 10.1016/j.it.2019.04.010.
  109. Xue, J., Zhao, Z., Zhang, L., Xue, L., Shen, S., Wen, Y., Wei, Z., Wang, L., Kong, L., Sun, H., Ping, Q., Mo, R., and Zhang, C. (2017) Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence, Nat. Nanotechnol., 12, 692-700, doi: 10.1038/nnano.2017.54.
  110. Ju, C., Wen, Y., Zhang, L., Wang, Q., Xue, L., Shen, J., and Zhang, C. (2019) Neoadjuvant Chemotherapy Based on Abraxane/Human Neutrophils Cytopharmaceuticals with Radiotherapy for Gastric Cancer, Small, 15, e1804191, doi: 10.1002/smll.201804191.
  111. Su, Y., Gao, J., Dong, X., Wheeler, K. A., and Wang, Z. (2023) Neutrophil-mediated delivery of nanocrystal drugs via photoinduced inflammation enhances cancer therapy, ACS Nano, 17, 15542-15555, doi: 10.1021/acsnano.3c02013.
  112. Dong, H., Li, Y., Liu, Y., Wen, Y., Zou, Z., Yang, T., Cui, Z., Shi, D., and Li, Y. (2019) A nano-immunotraining strategy to enhance the tumor targeting of neutrophils via in vivo pathogen-mimicking stimulation, Biomater. Sci., 7, 5238-5246, doi: 10.1039/c9bm01278h.
  113. Ye, B., Zhao, B., Wang, K., Guo, Y., Lu, Q., Zheng, L., Li, A., and Qiao, J. (2020) Neutrophils mediated multistage nanoparticle delivery for prompting tumor photothermal therapy, J. Nanobiotechnol., 18, 138, doi: 10.1186/s12951-020-00682-7.
  114. Li, C., Qiu, Q., Liu, M., Liu, X., Hu, L., Luo, X., Lai, C., Zhao, D., Zhang, H., Gao, X., Deng, Y., and Song, Y. (2020) Sialic acid-conjugate modified liposomes targeting neutrophils for improved tumour therapy, Biomater. Sci., 8, 2189-2201, doi: 10.1039/c9bm01732a.
  115. Luo, X., Liu, M., Hu, L., Qiu, Q., Liu, X., Li, C., Lu, M., Liu, Y., Zhang, T., Zhou, S., McClements, D. J., Jia, X., Deng, Y., and Song, Y. (2018) Targeted delivery of pixantrone to neutrophils by poly(sialic acid)-p-octadecylamine conjugate modified liposomes with improved antitumor activity, Int. J. Pharm., 547, 315-329, doi: 10.1016/j.ijpharm.2018.06.021.
  116. Fromen, C. A., Kelley, W. J., Fish, M. B., Adili, R., Noble, J., Hoenerhoff, M. J., Holinstat, M., and Eniola-Adefeso, O. (2017) Neutrophil-particle interactions in blood circulation drive particle clearance and alter neutrophil responses in acute inflammation, ACS Nano, 11, 10797-10807, doi: 10.1021/acsnano.7b03190.
  117. Naumenko, V., Nikitin, A., Garanina, A., Melnikov, P., Vodopyanov, S., Kapitanova, K., Potashnikova, D., Vishnevskiy, D., Alieva, I., Ilyasov, A., Eletskaya, B. Z., Abakumov, M., Chekhonin, V., and Majouga, A. (2020) Neutrophil-mediated transport is crucial for delivery of short-circulating magnetic nanoparticles to tumors, Acta Biomater., 104, 176-187, doi: 10.1016/j.actbio.2020.01.011.
  118. Naumenko, V. A., Vlasova, K. Y., Garanina, A. S., Melnikov, P. A., Potashnikova, D. M., Vishnevskiy, D. A., Vodopyanov, S. S., Chekhonin, V. P., Abakumov, M. A., and Majouga, A. G. (2019) Extravasating neutrophils open vascular barrier and improve liposomes delivery to tumors, ACS Nano, 13, 12599-12612, doi: 10.1021/acsnano.9b03848.
  119. Li, M., Li, S., Zhou, H., Tang, X., Wu, Y., Jiang, W., Tian, Z., Zhou, X., Yang, X., and Wang, Y. (2020) Chemotaxis-driven delivery of nano-pathogenoids for complete eradication of tumors post-phototherapy, Nat. Commun., 11, 1126, doi: 10.1038/s41467-020-14963-0.
  120. Chu, D., Zhao, Q., Yu, J., Zhang, F., Zhang, H., and Wang, Z. (2016) Nanoparticle targeting of neutrophils for improved cancer immunotherapy, Adv. Healthc. Mater., 5, 1088-1093, doi: 10.1002/adhm.201500998.
  121. Su, Y., Wang, T., Su, Y., Li, M., Zhou, J., Zhang, W., and Wang, W. (2020) A neutrophil membrane-functionalized black phosphorus riding inflammatory signal for positive feedback and multimode cancer therapy, Materials Horizons, 7, 574-585, doi: 10.1039/C9MH01068H.
  122. Zhang, Q., Dehaini, D., Zhang, Y., Zhou, J., Chen, X., Zhang, L., Fang, R. H., Gao, W., and Zhang, L. (2018) Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis, Nat. Nanotechnol., 13, 1182-1190, doi: 10.1038/s41565-018-0254-4.
  123. Cao, X., Hu, Y., Luo, S., Wang, Y., Gong, T., Sun, X., Fu, Y., and Zhang, Z. (2019) Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma, Acta Pharm. Sin. B, 9, 575-589, doi: 10.1016/j.apsb.2018.12.009.
  124. Cui, C., Chakraborty, K., Tang, X. A., Zhou, G., Schoenfelt, K. Q., Becker, K. M., Hoffman, A., Chang, Y. F., Blank, A., Reardon, C. A., Kenny, H. A., Vaisar, T., Lengyel, E., Greene, G., and Becker, L. (2021) Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis, Cell, 184, 3163-3177, e3121, doi: 10.1016/j.cell.2021.04.016.
  125. Zhang, C., Zhang, L., Wu, W., Gao, F., Li, R. Q., Song, W., Zhuang, Z. N., Liu, C. J., and Zhang, X. Z. (2019) Artificial super neutrophils for inflammation targeting and HClO generation against tumors and infections, Adv. Mater., 31, e1901179, doi: 10.1002/adma.201901179.
  126. McDermott, D. H., Velez, D., Cho, E., Cowen, E. W., DiGiovanna, J. J., Pastrana, D. V., Buck, C. B., Calvo, K. R., Gardner, P. J., Rosenzweig, S. D., Stratton, P., Merideth, M. A., Kim, H. J., Brewer, C., Katz, J. D., Kuhns, D. B., Malech, H. L., Follmann, D., Fay, M. P., and Murphy, P. M. (2023) A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome, J. Clin. Invest., 133, doi: 10.1172/JCI164918.
  127. Bilusic, M., Heery, C. R., Collins, J. M., Donahue, R. N., Palena, C., Madan, R. A., Karzai, F., Marte, J. L., Strauss, J., Gatti-Mays, M. E., Schlom, J., and Gulley, J. L. (2019) Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors, J. Immunother. Cancer, 7, 240, doi: 10.1186/s40425-019-0706-x.
  128. Melisi, D., Oh, D. Y., Hollebecque, A., Calvo, E., Varghese, A., Borazanci, E., Macarulla, T., Merz, V., Zecchetto, C., Zhao, Y., Gueorguieva, I., Man, M., Gandhi, L., Estrem, S. T., Benhadji, K. A., Lanasa, M. C., Avsar, E., Guba, S. C., and Garcia-Carbonero, R. (2021) Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer, J. Immunother. Cancer, 9, e002068, doi: 10.1136/jitc-2020-002068.

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
Жүктеу

© Russian Academy of Sciences, 2025

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».