Флуоресцентная время-разрешённая микроскопия в иммуноонкологии: мониторинг гетерогенности опухоли, клеточной гибели и динамики иммунного ответа
- Авторы: Хузина А.Р.1, Турубанова В.Д.1,2
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Учреждения:
- Научно-технологический университет «Сириус»
- Национальный исследовательский Нижегородский государственный университет имени Н.И. Лобачевского
- Выпуск: Том 20, № 4 (2025)
- Страницы: 296-310
- Раздел: Научные обзоры
- URL: https://journals.rcsi.science/2313-1829/article/view/381685
- DOI: https://doi.org/10.17816/gc678542
- EDN: https://elibrary.ru/OHCOJW
- ID: 381685
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Аннотация
Флуоресцентная микроскопия с временным разрешением (FLIM) активно развивается на протяжении последних двух десятилетий и играет значительную роль в биомедицинских исследованиях. Современные достижения в создании флуоресцентных зондов существенно расширили потенциал данного метода. Учитывая, что время жизни флуоресценции чувствительно к микросреде и молекулярным изменениям, FLIM представляет собой перспективный инструмент для выявления патологических состояний, включая онкологические заболевания. Эта технология позволяет наблюдать структуру опухоли и отслеживать динамические процессы в режиме реального времени, что дает возможность исследователям с поразительной точностью исследовать живые раковые клетки и их микроокружение. Более того, данный метод открывает новые возможности для мониторинга эффективности противоопухолевой терапии. Особый интерес представляет применение FLIM в разработке и оценке эффективности иммунотерапевтических стратегий. В контексте терапии солидных опухолей ключевое значение имеют данные о метаболизме и гетерогенности опухоли, механизмах клеточной гибели, а также о динамике иммунного ответа после терапевтического воздействия.
В настоящем обзоре на основании анализа современных научных данных мы обосновываем целесообразность использования FLIM в качестве важного инструмента в исследованиях, направленных на совершенствование методов иммунотерапии рака.
Ключевые слова
Об авторах
Алина Ринатовна Хузина
Научно-технологический университет «Сириус»
Email: huzinaar@gmail.com
ORCID iD: 0009-0007-9873-7471
Россия, Сириус
Виктория Дмитриевна Турубанова
Научно-технологический университет «Сириус»; Национальный исследовательский Нижегородский государственный университет имени Н.И. Лобачевского
Автор, ответственный за переписку.
Email: turubanova@neuro.nnov.ru
ORCID iD: 0000-0002-4648-0738
SPIN-код: 8262-6560
канд. биол. наук
Россия, Сириус; Нижний НовгородСписок литературы
- Ouyang Y, Liu Y, Wang ZM, et al. FLIM as a promising tool for cancer diagnosis and treatment monitoring. Nanomicro Lett. 2021;13(1):133. doi: 10.1007/s40820-021-00653-z EDN: UCHANB
- Datta R, Heaster TM, Sharick JT, et al. Fluorescence lifetime imaging microscopy: fundamentals and advances in instrumentation, analysis, and applications. J Biomed Opt. 2020;25(7):1–43. doi: 10.1117/1.JBO.25.7.071203 EDN: SETCAC
- Shirshin EA, Shirmanova MV, Gayer AV, et al. Label-free sensing of cells with fluorescence lifetime imaging: The quest for metabolic heterogeneity. Proc Natl Acad Sci U S A. 2022;119(9):e2118241119. doi: 10.1073/pnas.2118241119 EDN: DPJSCE
- Skala MC, Riching KM, Gendron-Fitzpatrick A, et al. In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia. Proc Natl Acad Sci U S A. 2007;104(49):19494–19499. doi: 10.1073/pnas.0708425104
- Blacker TS, Duchen MR, Bain AJ. NAD(P)H binding configurations revealed by time-resolved fluorescence and two-photon absorption. Biophys J. 2023;122(7):1240–1253. doi: 10.1016/j.bpj.2023.02.014 EDN: SFDCEO
- Huang S, Heikal AA, Webb WW. Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein. Biophys J. 2002;82(5):2811–2825. doi: 10.1016/S0006-3495(02)75621-X
- Komarova AD, Sinyushkina SD, Shchechkin ID, et al. Insights into metabolic heterogeneity of colorectal cancer gained from fluorescence lifetime imaging. Elife. 2024;13. doi: 10.7554/eLife.94438 EDN: VKZMQV
- Zhang J, Wallrabe H, Siller K, et al. Measuring metabolic changes in cancer cells using two-photon fluorescence lifetime imaging microscopy and machine-learning analysis. J Biophotonics. 2025;18(1):e202400426. doi: 10.1002/jbio.202400426 EDN: ZFNBTW
- Hao L, Li ZW, Zhang DY, et al. Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging. Chem Sci. 2018;10(5):1285–1293. doi: 10.1039/c8sc04242j
- Rahim MK, Zhao J, Patel HV, et al. Phasor analysis of fluorescence lifetime enables quantitative multiplexed molecular imaging of three probes Anal Chem. 2022;94(41):14185–14194. doi: 10.1021/acs.analchem.2c02149 EDN: MPDSXC
- Goryashchenko AS, Pakhomov AA, Ryabova AV, et al. FLIM-based intracellular and extracellular ph measurements using genetically encoded ph sensor. Biosensors (Basel). 2021;11(9):340. doi: 10.3390/bios11090340 EDN: DDUOOI
- Zlobovskaya OA, Sergeeva TF, Shirmanova MV, et al. Genetically encoded far-red fluorescent sensors for Caspase-3 activity. 2016;60(2):62–68. doi: 10.2144/000114377 EDN: WRSBPB
- Sagar MAK, Cheng KP, Ouellette JN, et al. Machine learning methods for fluorescence lifetime imaging (FLIM) based label-free detection of microglia. Front Neurosci. 2020;14:931. doi: 10.3389/fnins.2020.00931 EDN: LASDPQ
- Shchechkin ID. Recent trends of fluorescence lifetime imaging microscopy analysis using machine learning. Journal of Biomedical Photonics & Engineering. 2025;11(1):010201. doi: 10.18287/JBPE25.11.010201 EDN: UHYICS
- Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31–46. doi: 10.1158/2159-8290.CD-21-1059 EDN: LPSAUZ
- Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674. doi: 10.1016/j.cell.2011.02.013 EDN: OAGZMH
- Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309–314. doi: 10.1126/science.123.3191.309 EDN: ICRUGV
- Eggert D, Gaertner D, Rühm A, et al. Differentiation of tumors of the upper respiratory tract using optical metabolic imaging. Lasers Surg Med. 2025;57(2):147–153. doi: 10.1002/lsm.23870 EDN: PTJNSI
- Lukina M, Yashin K, Kiseleva EE, et al. Label-free macroscopic fluorescence lifetime imaging of brain tumors. Front Oncol. 2021;11:666059. doi: 10.3389/fonc.2021.666059 EDN: CWIFPJ
- Vander Heiden MG, DeBerardinis RJ. Understanding the intersections between metabolism and cancer biology. Cell. 2017;168(4):657–669. doi: 10.1016/j.cell.2016.12.039
- Jia D, Park JH, Jung KH, et al. Elucidating the metabolic plasticity of cancer: mitochondrial reprogramming and hybrid metabolic states. Cells. 2018;7(3):21. doi: 10.3390/cells7030021
- Pickett MR, Chen YI, Kamra M, et al. Assessing the impact of extracellular matrix fiber orientation on breast cancer cellular metabolism. Cancer Cell Int. 2024;24(1):199. doi: 10.1186/s12935-024-03385-3 EDN: GMKPME
- Karrobi K, Tank A, Fuzail MA, et al. Fluorescence lifetime imaging microscopy (flim) reveals spatial-metabolic changes in 3D breast cancer spheroids. Sci Rep. 2023;13(1):3624. doi: 10.1038/s41598-023-30403-7 EDN: PCWEGO
- Gershanov S, Michowiz S, Toledano H, et al. Fluorescence lifetime imaging microscopy, a novel diagnostic tool for metastatic cell detection in the cerebrospinal fluid of children with medulloblastoma. Sci Rep. 2017;7(1):3648. doi: 10.1038/s41598-017-03892-6 EDN: YICPNG
- Yahav G, Hirshberg A, Salomon O, et al. Fluorescence lifetime imaging of DAPI-stained nuclei as a novel diagnostic tool for the detection and classification of B-cell chronic lymphocytic leukemia. Cytometry A. 2016;89(7):644–652. doi: 10.1002/cyto.a.22890
- Zahavi T, Yahav G, Shimshon Y, et al. Utilizing fluorescent life time imaging microscopy technology for identify carriers of BRCA2 mutation. Biochem Biophys Res Commun. 2016;480(1):36–41. doi: 10.1016/j.bbrc.2016.10.013
- Dong L, Neuzil J. Targeting mitochondria as an anticancer strategy. Cancer Commun (Lond). 2019;39(1):63. doi: 10.1186/s40880-019-0412-6 EDN: WZMBNV
- Morelli M, Lessi F, Barachini S, et al. Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early. Front Oncol. 2022;12:969812. doi: 10.3389/fonc.2022.969812 EDN: CXKNSF
- Yuzhakova DV, Sachkova DA, Shirmanova MV, et al. Measurement of patient-derived glioblastoma cell response to temozolomide using fluorescence lifetime imaging of NAD(P)H. Pharmaceuticals (Basel). 2023;16(6):796. doi: 10.3390/ph16060796 EDN: HBEKML
- Lukina MM, Dudenkova VV, Ignatova NI, et al. Metabolic cofactors NAD(P)H and FAD as potential indicators of cancer cell response to chemotherapy with paclitaxel. Biochim Biophys Acta Gen Subj. 2018;1862(8):1693–1700. doi: 10.1016/j.bbagen.2018.04.021 EDN: XXFNIL
- Druzhkova I, Nikonova E, Ignatova N, et al. Effect of collagen matrix on doxorubicin distribution and cancer cells’ response to treatment in 3D tumor model. Cancers (Basel). 2022;14(22):5487. doi: 10.3390/cancers14225487 EDN: VQRNCH
- Alam SR, Wallrabe H, Svindrych Z, et al. Investigation of mitochondrial metabolic response to doxorubicin in prostate cancer cells: An NADH, FAD and tryptophan FLIM assay. Sci Rep. 2017;7(1):10451. doi: 10.1038/s41598-017-10856-3 EDN: YHLKTA
- Shakirova JR, Baigildin VA, Solomatina AI, et al. Intracellular PH sensor based on heteroleptic bis-cyclometalated Iridium(III) complex embedded into block-copolymer nanospecies: application in phosphorescence lifetime imaging microscopy. Advanced Functional Materials. 2023;33. doi: 10.1002/adfm.202212390 EDN: DSBSUW
- Druzhkova I, Komarova A, Nikonova E, et al. Monitoring the intracellular pH and metabolic state of cancer cells in response to chemotherapy using a combination of phosphorescence lifetime imaging microscopy and fluorescence lifetime imaging microscopy. International Journal of Molecular Sciences. 2023;25:49. doi: 10.3390/ijms25010049 EDN: RPOFMC
- González Rubio S, Montero Pastor N, García C, et al. Enhanced cytotoxic activity of mitochondrial mechanical effectors in human lung carcinoma H520 cells: pharmaceutical implications for cancer therapy. Front Oncol. 2018;8:514. doi: 10.3389/fonc.2018.00514 EDN: GOSVQC
- Gillette AA, Babiarz CP, VanDommelen AR, et al. Autofluorescence imaging of treatment response in neuroendocrine tumor organoids. Cancers (Basel). 2021;13(8):1873. doi: 10.3390/cancers13081873 EDN: DICIVR
- Walsh AJ, Cook RS, Sanders ME, et al. Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Cancer Res. 2014;74(18):5184–5194. doi: 10.1158/0008-5472.CAN-14-0663
- Walsh AJ, Castellanos JA, Nagathihalli NS, et al. Optical imaging of drug-induced metabolism changes in murine and human pancreatic cancer organoids reveals heterogeneous drug response. Pancreas. 2016;45(6):863–869. doi: 10.1097/MPA.0000000000000543
- Sharick JT, Walsh CM, Sprackling CM, et al. Metabolic heterogeneity in patient tumor-derived organoids by primary site and drug treatment. Front Oncol. 2020;10:553. doi: 10.3389/fonc.2020.00553 EDN: MWLSCQ
- Pasch CA, Favreau PF, Yueh AE, et al. Patient-derived cancer organoid cultures to predict sensitivity to chemotherapy and radiation. Clin Cancer Res. 2019;25(17):5376–5387. doi: 10.1158/1078-0432.CCR-18-3590
- Moloudi K, Abrahamse H, George BP. Photodynamic therapy induced cell cycle arrest and cancer cell synchronization: review. Front Oncol. 2023;13:1225694. doi: 10.3389/fonc.2023.1225694 EDN: LKGHPR
- Zhou R, Zeng X, Zhao H, et al. Combating the hypoxia limit of photodynamic therapy through reversing the survival-related pathways of cancer cells. Coordination Chemistry Reviews. 2022;452:214306. doi: 10.1016/j.ccr.2021.214306 EDN: HWZEWP
- Dos Santos DNS, Naskar N, Delgado-Pinar E, et al. Bromine indirubin FLIM/PLIM sensors to measure oxygen in normoxic and hypoxic PDT conditions. Photodiagnosis Photodyn Ther. 2024;45:103964. doi: 10.1016/j.pdpdt.2024.103964 EDN: MTVTGA
- Kalinina S, Breymayer J, Reeß K, et al. Correlation of intracellular oxygen and cell metabolism by simultaneous PLIM of phosphorescent TLD1433 and FLIM of NAD(P)H. J Biophotonics. 2018;11(10):e201800085. doi: 10.1002/jbio.201800085 EDN: QOOHKH
- Bassler MC, Hiller J, Wackenhut F, et al. Fluorescence lifetime imaging unravels the pathway of glioma cell death upon hypericin-induced photodynamic therapy. RSC Chem Biol. doi: 10.1039/d4cb00107a EDN: APXDGY
- Shimolina LE, Khlynova AE, Elagin VV, et al. Unraveling microviscosity changes induced in cancer cells by photodynamic therapy with targeted genetically encoded photosensitizer. Biomedicines. 2024;12(11):2550. doi: 10.3390/biomedicines12112550 EDN: LGXQBZ
- Chen B, Pogue BW, Hoopes PJ, Hasan T. Vascular and cellular targeting for photodynamic therapy. Crit Rev Eukaryot Gene Expr. 2006;16(4):279–305. doi: 10.1615/critreveukargeneexpr.v16.i4.10 EDN: MESOQP
- Domka W, Bartusik-Aebisher D, Mytych W, et al. The use of photodynamic therapy for head, neck, and brain diseases. Int J Mol Sci. 2023;24(14):11867. doi: 10.3390/ijms241411867 EDN: YVZDBT
- Shirmanova MV, Lukina MM, Sirotkina MA, et al. Effects of photodynamic therapy on tumor metabolism and oxygenation revealed by fluorescence and phosphorescence lifetime imaging. Int J Mol Sci. 2024;25(3):1703. doi: 10.3390/ijms25031703 EDN: OWBHSK
- Belashov AV, Zhikhoreva AA, Salova AV, et al. PDT-induced variations of radachlorin fluorescence lifetime in living cells in vitro. Photonics. 2023;10(11):1262. doi: 10.3390/photonics10111262 EDN: JATPOE
- Shah AT, Demory Beckler M, Walsh AJ, et al. Optical metabolic imaging of treatment response in human head and neck squamous cell carcinoma. PLoS One. 2014;9:e90746. doi: 10.1371/journal.pone.0090746
- Shah AT, Diggins KE, Walsh AJ, et al. In vivo autofluorescence imaging of tumor heterogeneity in response to treatment. Neoplasia. 2015;17(12):862–870. doi: 10.1016/j.neo.2015.11.006
- Qi X, Li Q, Che X, et al. Application of regulatory cell death in cancer: based on targeted therapy and immunotherapy. Front Immunol. 2022;13:837293. doi: 10.3389/fimmu.2022.837293 EDN: HYYEFX
- Liu J, Hong M, Li Y, et al. Programmed cell death tunes tumor immunity. Front Immunol. 2022;13:847345. doi: 10.3389/fimmu.2022.847345 EDN: VYRPKM
- Yu L, Huang K, Liao Y, et al. Targeting novel regulated cell death: Ferroptosis, pyroptosis and necroptosis in anti-PD-1/PD-L1 cancer immunotherapy. Cell Prolif. 2024;57(8):e13644. doi: 10.1111/cpr.13644 EDN: CMXQBA
- Shirmanova MV, Gavrina AI, Kovaleva TF, et al. Insight into redox regulation of apoptosis in cancer cells with multiparametric live-cell microscopy. Sci Rep. 2022;12(1):4476. doi: 10.1038/s41598-022-08509-1 EDN: WRZYJF
- Bower AJ, Sorrells JE, Li J, et al. Tracking metabolic dynamics of apoptosis with high-speed two-photon fluorescence lifetime imaging microscopy. Biomed Opt Express. 2019;10(12):6408–6421. doi: 10.1364/BOE.10.006408
- Pan W, Qu J, Chen T, et al. FLIM and emission spectral analysis of caspase-3 activation inside single living cell during anticancer drug-induced cell death. Eur Biophys J. 2009;38(4):447–456. doi: 10.1007/s00249-008-0390-0 EDN: LVTYAN
- Xiao A, Gibbons AE, Luker KE, Luker GD. Fluorescence lifetime imaging of apoptosis. Tomography. 2015;1(2):115–124. doi: 10.18383/j.tom.2015.00163
- Liu Q, Osterlund EJ, Chi X, et al. Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2. Elife. 2019;8. doi: 10.7554/eLife.37689
- Buytaert E, Callewaert G, Vandenheede JR, Agostinis P. Deficiency in apoptotic effectors BAX and BAK reveals an autophagic cell death pathway initiated by photodamage to the endoplasmic reticulum. Autophagy. 2006;2(3):238–240. doi: 10.4161/auto.2730
- Kessel D, Vicente MG, Reiners JJ Jr. Initiation of apoptosis and autophagy by photodynamic therapy. Lasers Surg Med. 2006;38(5):482–488. doi: 10.1002/lsm.20334
- Ciccarone F, Di Leo L, Lazzarino G, et al. Aconitase 2 inhibits the proliferation of MCF-7 cells promoting mitochondrial oxidative metabolism and ROS/FoxO1-mediated autophagic response. Br J Cancer. 2020;122(2):182–193. doi: 10.1038/s41416-019-0641-0 EDN: UKYBPZ
- Li M, Chen Y, He W, Guo Z. Fluorescence and lifetime imaging of endoplasmic reticulum polarity change during ferroptosis. Chemistry. 2024;30(35):e202401285. doi: 10.1002/chem.202401285 EDN: ROUPXM
- Liang X, Zhao Y, Yan J, et al. Mechanosensitive fluorescence lifetime probes for investigating the dynamic mechanism of ferroptosis. Proc Natl Acad Sci U S A. 2024;121(41):e2316450121. doi: 10.1073/pnas.2316450121 EDN: NLGMPU
- Wang Y, Gao W, Shi X, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017;547(7661):99–103. doi: 10.1038/nature22393 EDN: TOILOK
- Wei X, Xie F, Zhou X, et al. Role of pyroptosis in inflammation and cancer. Cell Mol Immunol. 2022;19(9):971–992. doi: 10.1038/s41423-022-00905-x EDN: MWJHZD
- Jiang S, Qin K, Sun L. Time-lapse live-cell imaging of pyroptosis by confocal microscopy. STAR Protoc. 2023;4(4):102708. doi: 10.1016/j.xpro.2023.102708 EDN: HEQZMD
- Huang P, Chen G, Jin W, et al. Molecular mechanisms of parthanatos and its role in diverse diseases. Int J Mol Sci. 2022;23(13):7292. doi: 10.3390/ijms23137292 EDN: NKGKXH
- Brosey CA, Ho C, Long WZ, et al. Defining NADH-driven allostery regulating apoptosis-inducing factor. Structure. 2016;24(12):2067–2079. doi: 10.1016/j.str.2016.09.012 EDN: FECQWH
- van der Windt GJ, Pearce EL. Metabolic switching and fuel choice during T-cell differentiation and memory development. Immunol Rev. 2012;249(1):27–42. doi: 10.1111/j.1600-065X.2012.01150.x EDN: ROLHEV
- Patel M, Manzella-Lapeira J, Akkaya M. Analysis of mitochondrial performance in lymphocytes using fluorescent lifetime imaging microscopy. Methods Mol Biol. 2022;2497:269–280. doi: 10.1007/978-1-0716-2309-1_17
- Floudas A, Neto N, Orr C, et al. Loss of balance between protective and pro-inflammatory synovial tissue T-cell polyfunctionality predates clinical onset of rheumatoid arthritis. Ann Rheum Dis. 2022;81(2):193–205. doi: 10.1136/annrheumdis-2021-220458 EDN: TAPESF
- Walsh AJ, Mueller KP, Tweed K, et al. Classification of T-cell activation via autofluorescence lifetime imaging. Nat Biomed Eng. 2021;5(1):77–88. doi: 10.1038/s41551-020-0592-z EDN: AUGTEY
- Paillon N, Ung TPL, Dogniaux S, et al. Label-free single-cell live imaging reveals fast metabolic switch in T lymphocytes. Mol Biol Cell. 2024;35(1):ar11. doi: 10.1091/mbc.E23-01-0009 EDN: JKVLRT
- Izosimova AV, Shirmanova MV, Shcheslavskiy VI, et al. FLIM of NAD(P)H in lymphatic nodes resolves T-cell immune response to the tumor. Int J Mol Sci. 2022;23(24):15829. doi: 10.3390/ijms232415829 EDN: DYPCGJ
- Pavillon N, Hobro AJ, Akira S, Smith NI. Noninvasive detection of macrophage activation with single-cell resolution through machine learning. Proc Natl Acad Sci U S A. 2018;115(12):E2676–E2685. doi: 10.1073/pnas.1711872115
- Alfonso-García A, Smith TD, Datta R, et al. Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy. J Biomed Opt. 2016;21(4):46005. doi: 10.1117/1.JBO.21.4.046005
- Sheikh E, Agrawal K, Roy S, et al. Multimodal imaging of pancreatic cancer microenvironment in response to an antiglycolytic drug. Adv Healthc Mater. 2023;12(31):e2301815. doi: 10.1002/adhm.202301815 EDN: TVSMNE
- Szulczewski JM, Inman DR, Entenberg D, et al. In vivo visualization of stromal macrophages via label-free FLIM-based metabolite imaging. Sci Rep. 2016;6:25086. doi: 10.1038/srep25086
- Kanno H, Hiramatsu K, Mikami H, et al. High-throughput fluorescence lifetime imaging flow cytometry. Nat Commun. 2024;15(1):7376. doi: 10.1038/s41467-024-51125-y EDN: HSBJAN
- Wang S, Luo C, Guo J, et al. Enhancing therapeutic response and overcoming resistance to checkpoint inhibitors in ovarian cancer through cell cycle regulation. Int J Mol Sci. 2024;25(18):10018. doi: 10.3390/ijms251810018 EDN: VNWUDJ
- Yang M, Mahanty A, Jin C, et al. Label-free metabolic imaging for sensitive and robust monitoring of anti-CD47 immunotherapy response in triple-negative breast cancer. J Immunother Cancer. 2022;10(9):e005199. doi: 10.1136/jitc-2022-005199 EDN: TWCNKE
- Izosimova AV, Mozherov AM, Shirmanova MV, et al. Fluorescence lifetime imaging of NAD(P)H T cells autofluorescence in the lymphatic nodes to assess the effectiveness of anti-CTLA-4 immunotherapy. Modern technologies in medicine. 2023;15(30):5–15. doi: 10.17691/stm2023.15.3.01 EDN: UFWPEQ
- Yuzhakova DV, Sachkova DA, Izosimova AV, et al. Fluorescence lifetime imaging of NAD(P)H in patients’ lymphocytes: evaluation of efficacy of immunotherapy. Cells. 2025;14(2):97. doi: 10.3390/cells14020097 EDN: QIXLYU
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