Expression of Immune Checkpointson T-Lymphocytes in Regional Lymph Nodes in Patients With Colorectal Cancer
- Authors: Kryukova V.V.1, Tsepelev V.L.1, Tereshkov P.P.1
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Affiliations:
- Chita State Medical Academy
- Issue: Vol 106, No 3 (2025)
- Pages: 341-348
- Section: Theoretical and clinical medicine
- Submitted: 22.01.2025
- Accepted: 11.03.2025
- Published: 30.05.2025
- URL: https://kazanmedjournal.ru/kazanmedj/article/view/646505
- DOI: https://doi.org/10.17816/KMJ646505
- EDN: https://elibrary.ru/UXXNJY
- ID: 646505
Cite item
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
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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, 672000Viktor 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, 672000Pavel 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, 672000References
- Arasa J, Collado-Diaz V, Halin C. Structure and immune function of afferent lymphatics and their mechanistic contribution to dendritic cell and T cell trafficking. Cells. 2021;10(5):1269. doi: 10.3390/cells10051269 EDN: IBMPJF
- Lei PJ, Fraser C, Jones D, et al. Lymphatic system regulation of anti-cancer immunity and metastasis. Front Immunol. 2024;15:1449291. doi: 10.3389/fimmu.2024.1449291 EDN: WTIORR
- Zheng Z, Wieder T, Mauerer B, et al. T cells in colorectal cancer: unravelling the function of different T cell subsets in the tumor microenvironment. Int J Mol Sci. 2023;24(14):11673. doi: 10.3390/ijms241411673 EDN: MMPGVR
- Morisaki T, Morisaki T, Kubo M, et al. Lymph nodes as anti-tumor immunotherapeutic tools: intranodal-tumor-specific antigen-pulsed dendritic cell vaccine immunotherapy. Cancers. 2022;14(10):2438. doi: 10.3390/cancers14102438 EDN: VLNLUH
- Goode EF, Roussos Torres ET, Irshad S. Lymph node immune profiles as predictive biomarkers for immune checkpoint inhibitor response. Front Mol Biosci. 2021;8:674558. doi: 10.3389/fmolb.2021.674558 EDN: EHYQZH
- Fransen MF, van Hall T, Ossendorp F. Immune checkpoint therapy: tumor draining lymph nodes in the spotlights. Int J Mol Sci. 2021;22:9401. doi: 10.3390/ijms22179401 EDN: JHZXWH
- Zhang Y, Zheng J. Functions of immune checkpoint molecules beyond immune evasion. Adv Exp Med Biol. 2020;1248:201–226. doi: 10.1007/978-981-15-3266-5_9
- Zhang H, Dai Z, Wu W, et al. Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer. J Exp Clinic Cancer Res. 2021;40(1):184. doi: 10.1186/s13046-021-01987-7 EDN: TEVMDU
- Saleh R, Taha RZ, Toor SM, et al. Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer. Cancer Immunology, Immunotherapy. 2020;69:1989–1999. doi: 10.1007/s00262-020-02593-w EDN: FUYBXJ
- Chetveryakov AV, Tsepelev VL. Level of co-inhibitory immune checkpoints in tumor tissue in patients with colon neoplasms. Mol Med. 2023;21(1):56–60. doi: 10.29296/24999490-2023-01-08
- Chetveryakov AV, Tsepelev VL. Concentration of co-inhibitory immune checkpoints and their ligands in the blood of patients with colon tumor. Pathological physiology and experimental therapy. 2023;67(1):56–62. doi: 10.25557/0031-2991.2023.01.56-62 EDN: HDLEXN
- Xie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 2020;5(1):1–30. doi: 10.1038/s41392-020-0116-z EDN: DCYDFN
- Kudryavtsev IV, Borisov AG, Krobinets II, et al. Determination of the main subpopulations of cytotoxic T-lymphocytes by multicolor flow cytometry. Medical Immunology. 2015;17(6):525–538. doi: 10.15789/1563-0625-2015-6-525-538
- Mudrov VA. Algorithm for applying roc-analysis in biomedical research using the SPSS software package. Transbaikal Medical Bulletin. 2021;1:148–153. doi: 10.52485/19986173_2021_1_148
- Van Coillie S, Wiernicki B, Xu J. Molecular and cellular functions of CTLA-4. Adv Exp Med Biol. 2020;1248:7–32. doi: 10.1007/978-981-15-3266-5_2 EDN: CNNTKJ
- Kanunova TA, Makarova YuA, Belova LA, Shamrova EA. Pathophysiological mechanisms of the use of checkpoint inhibitors in the regulation of the antitumor immune response. Scientific review. Medical Sciences. 2020;4:33–37. EDN: QYXMUZ
- Pauken KE, Torchia JA, Chaudhri A, et al. Emerging concepts in PD-1 checkpoint biology. Semin Immunol. 2021;52:101480. doi: 10.1016/j.smim.2021.101480 EDN: UVBAWR
- Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020;10(3):727. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7136921/
- Acharya N, Sabatos-Peyton C, Anderson AC. Tim-3 finds its place in the cancer immunotherapy landscape. J Immunother Cancer. 2020;8(1):000911. doi: 10.1136/jitc-2020-000911 EDN: NGEVXE
- Joller N, Anderson AC, Kuchroo VK. LAG-3, TIM-3, and TIGIT: distinct functions in immune regulation. Immunity. 2024;57(2):206–222. doi: 10.1016/j.immuni.2024.01.010 EDN: OEDHIT
- Hossain MA, Liu G, Dai B, et al. Reinvigorating exhausted CD8+ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy. Med Res Rev. 2021;41(1):156–201. doi: 10.1002/med.21727 EDN: RKQBGZ
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