Changes in the subpopulation composition of tumor-infiltrating cytotoxic Т-lymphocytes and the expression of co-inhibitory molecules on their surface in stage III colorectal cancer

Abstract

Relevance: Studying the subpopulation composition of cytotoxic T-lymphocytes and the expression of co-inhibitory proteins on their surface in the tumor microenvironment is necessary for the development of new methods of targeted therapy for colorectal cancer (CRC). Aim: To study the subpopulation composition of cytotoxic T-lymphocytes and the expression of co-inhibitory molecules on their surface in the primary tumor growth site in patients with stage III colon cancer. Methods. The relative content of cytotoxic T-lymphocytes in the tumor microenvironment, the subpopulation composition of cytotoxic T-lymphocytes, as well as the expression of immune checkpoints (CTLA-4, PD-1, TIM-3) by CD8-positive cells were measured in 105 patients with stage III CRC by flow cytometry. The control group consisted of 75 patients who underwent colon surgery for non-neoplastic diseases. Results. In patients with stage III CRC, the proportion of naive cells (CD3+CD8+CD45RA+CCR7+) in the primary tumor growth site was decreased by 23.1%; the relative content of cytotoxic T-lymphocytes of central memory (CD3+CD8+CD45RA-CCR7+) and effector memory (CD3+CD8+CD45RA-ССR7-) was increased by 1.5 and 1.4 times, respectively; and the number of terminally differentiated T-cells (CD3+CD8+CD45RA+ССR7-) was decreased. In CRC patients, on the surface of CD3+CD8+ lymphocytes in the tumor microenvironment, the expression of CD57 was increased by 1.9 times, the co-inhibitory CTLA-4 molecule by 1.9 times, and the TIM-3 protein by 2.5 times. Conclusion. In patients with stage III CRC, the subpopulation composition of tumor-infiltrating cytotoxic T lymphocytes changes, which is evident as a decreased proportion of naive and terminally differentiated T cells along with an increase in the percentage of central and effector memory cells. In stage III CRC, the expression of co-inhibitory molecules (CTLA-4 and TIM-3) on cytotoxic T lymphocytes of the tumor microenvironment increases.