Expression of Immune Checkpointson T-Lymphocytes in Regional Lymph Nodes in Patients With Colorectal Cancer

Abstract

BACKGROUND: Investigation of immune checkpoint expression on T-lymphocytes is essential for determining immunotherapy strategies for colorectal cancer.

AIM: The work aimed to examine the expression of immune checkpoints on T-lymphocytes in regional lymph nodes in patients with colorectal cancer.

MATERIAL AND METHODS: Flow cytometry was used to evaluate the expression levels of immune checkpoints (CTLA-4, PD-1, TIM-3) on T-lymphocytes in regional lymph nodes in 105 patients with stage III colorectal cancer. The control group included 75 patients with nonneoplastic colon diseases. The Mann–Whitney U-test was used to compare two independent groups. ROC analysis was performed to identify diagnostic threshold values. Differences were considered statistically significant at p < 0.05.

RESULTS: In the regional lymph nodes of patients with colorectal cancer, CTLA-4 expression increased 7.9-fold on T-helper cells [42.9% (25.1%–59.8%) in the main group vs 5.4% (2.8%–7.8%) in controls; p < 0.001], and 4.5-fold on cytotoxic T-lymphocytes [35.0% (16.9%–52.8%) vs 7.8% (3.5%–12.7%); p < 0.001]. PD-1 expression increased 1.5-fold on CD4-positive T-lymphocytes [46.9 (33.5; 62.9)% in the main group vs 31.7 (18.9; 42.7)% in controls, p < 0.001], and 2.2-fold on cytotoxic T-lymphocytes (p < 0.001). TIM-3 expression on cytotoxic T-lymphocytes in regional lymph nodes reached 3.8 (2.3; 6.6)% in patients with colorectal cancer, exceeding the control value of 2.3 (1.5; 4.1)% by 1.7 times (p < 0.001). Statistically significant threshold values for CTLA-4 expression in regional lymph nodes were established at ≥ 11.1% for T-helper cells and > 20.1% for cytotoxic T-lymphocytes.

CONCLUSION: In patients with colorectal cancer, the expression of the co-inhibitory receptors CTLA-4 and PD-1 is increased on both T-helper cells and cytotoxic T-lymphocytes in regional lymph nodes, whereas TIM-3 expression is elevated on CD8+ T-lymphocytes.

Keywords

colorectal cancer / lymph nodes / T-lymphocytes / immune checkpoints

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