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

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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.

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About the authors

Victoria V. Kryukova

Chita State Medical Academy

Email: oigen72@yandex.ru
ORCID iD: 0009-0008-2228-3351
SPIN-code: 7136-0110

MD, Cand. Sci. (Medicine), Assistant Professor, Depart. of Hospital Surgery with a Course in Pediatric Surgery

Russian Federation, 39a Gorky st, Chita, 672000

Viktor L. Tsepelev

Chita State Medical Academy

Author for correspondence.
Email: viktorcepelev@mail.ru
ORCID iD: 0000-0002-2166-5154
SPIN-code: 4624-4537
Scopus Author ID: 55548678900
ResearcherId: MCJ-0526-2025

MD, Dr. Sci. (Medicine), Professor, Head, Depart. of Hospital Surgery with a Course in Pediatric Surgery

Russian Federation, 39a Gorky st, Chita, 672000

Pavel P. Tereshkov

Chita State Medical Academy

Email: tpp6915@mail.ru
ORCID iD: 0000-0002-8601-3499
SPIN-code: 5228-8808

MD, Cand. Sci. (Medicine), Head, Lab. of Experimental and Clinical Biochemistry and Immunology

Russian Federation, 39a Gorky st, Chita, 672000

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2. Fig. 1. CTLA-4 expression on T lymphocytes of regional lymph nodes in patients with colorectal cancer. The results are presented as box plots showing the median, interquartile range (Q1–Q3), and minimum and maximum values.

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3. Fig. 2. PD-1 expression on T lymphocytes of regional lymph nodes in patients with colorectal cancer. The results are presented as box plots showing the median, interquartile range (Q1–Q3), and minimum and maximum values.

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4. Fig. 3. TIM-3 expression on T lymphocytes of regional lymph nodes in patients with colorectal cancer. The results are presented as box plots showing the median, interquartile range (Q1–Q3), and minimum and maximum values.

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