Expression of immune checkpoints by tumor microenvironment Т-lymphocytes in colon cancer

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Abstract

The study of immune checkpoint expression by tumor microenvironment T-lymphocytes is necessary for understanding the pathophysiological mechanisms of tumor immunosuppression, as well as for the development of new methods of targeted therapy for colorectal cancer (CRC).

Objective. To study the expression of immune checkpoints by T-lymphocytes in the tumor microenvironment of patients with colon cancer.

Material and methods. The level of expression of immune checkpoints (CTLA-4, PD-1, TIM-3) by tumor microenvironment T-lymphocytes in 105 patients with stage III colorectal cancer was studied using flow cytometry. The control group consisted of 75 patients with non-neoplastic diseases of the colon.

Results. In patients with CRC, the expression of the co-inhibitory protein CTLA-4 on T-helpers increases by 5.5 times and on cytotoxic T-lymphocytes of the tumor microenvironment by 1.9 times. The level of PD-1 expression by CD4-positive T-lymphocytes in the group of patients with CRC exceeds the similar indicator in the control group by 1.8 times. In CRC, the relative content of CD8+TIM-3+ lymphocytes in the tumor microenvironment is 2.5 times higher than the similar indicator in the control group. A statistically significant threshold for exceeding the level of CTLA-4, PD-1 and TIM-3 protein expression on the surface of T-lymphocytes of the tumor microenvironment in colorectal cancer relative to the control group was established. For the CTLA-4 protein, this indicator was 14.7% or more on T-helpers, for the PD-1 molecule – more than 41.9% on CD4-positive lymphocytes and TIM-3+ – more than 6.1% on cytotoxic T-lymphocytes.

Conclusion. In patients with colon cancer, the expression of the co-inhibitory protein CTLA-4 on the surface of both T-helpers and cytotoxic T-lymphocytes, the PD-1 molecule on CD4-positive cells and TIM-3 on CD8+ lymphocyte increases in the primary tumor site.

About the authors

Victoria V. Kryukova

Chita State Medical Academy

Email: oigen72@yandex.ru
ORCID iD: 0009-0008-2228-3351

Associate Professor of the Department of Hospital Surgery with a Course in Pediatric Surgery, Candidate of Medical Sciences

Russian Federation, Gorky St. 39a, Chita, 672000

Viktor L. Tsepelev

Chita State Medical Academy

Email: viktorcepelev@mail.ru
ORCID iD: 0000-0002-2166-5154

Head of the Department of Hospital Surgery with a Course in Pediatric Surgery, Doctor of Medical Sciences, Professor

Russian Federation, Gorky St. 39a, Chita, 672000

Pavel P. Tereshkov

Chita State Medical Academy

Author for correspondence.
Email: tpp6915@mail.ru
ORCID iD: 0000-0002-8601-3499

Head of the Laboratory of Experimental and Clinical Biochemistry and Immunology, Research Institute of Molecular Medicine, Candidate of Medical Sciences

Russian Federation, Gorky St. 39a, Chita, 672000

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