Activity of the 4-1BB/4-1BBL signaling pathway in patients with colon tumors

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Abstract

Background. Protein 4-1BB (CD137) enhances the activity of T-cells, prevents their death, and promotes the production of cytokines, which makes it a powerful co-stimulating agent. Currently, the use of this glycoprotein is being studied in order to influence the key links of carcinogenesis. Objective. We aimed to assess 4-1BB level in blood serum, tumor tissue and lymph nodes in patients with colon tumors. Methods. The study was carried out in the Regional Oncology Dispensary in Chita and included 44patients with colorectal cancer and 25 patients with benign tumor of the colon who were treated between 2019 to 2020. The control group comprised 25 patients who had been operated due to colon injury at the Regional Clinical Hospital in Chita. We determined 4-1BB concentration in blood serum, the supernatant of the homogenate of tumor tissue and lymph nodes using the flow cytofluometry method. Results. It was found that in patients with colon cancer the concentration of the soluble form 4-1BB in the blood serum increased by 1.88 times, in patients with benign tumor of the colon - by 1.86 times compared to the control group. The concentration of 4-1BB in tumor tissue in patients with colorectal cancer exceeded this indicator by 2.06 times compared to the control group and it increased by 1.43 times in comparison with the group of patients with benign tumor. Conclusion. The 4-1BB/4-1BBL signaling pathway is involved in the cascade of innate and acquired immunity reactions and is one of the carcinogenesis links in patients with colorectal cancer.

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About the authors

Andrey Valerevich Chetveryakov

FSBI HE “Chita State Medical Academy”, Ministry of Health of Russia

Email: yasnogorsk94@gmail.com

postgraduate, Department of Hospital Surgery

Russian Federation,

Viktor Lvovich Tsepelev

FSBI HE “Chita State Medical Academy”, Ministry of Health of Russia

Author for correspondence.
Email: viktorcepelev@mail.ru

Head of the Department of Hospital Surgery

Russian Federation,

References

  1. Fan X., Wang D., Zhang W., Liu J., Liu C., Li Q., Ma Z., Li H., Guan X., Bai Y. Inflammatory markers predict survival in patients with advanced gastric and colorectal cancers receiving Anti-PD-1 therapy. Front Cell Dev Biol. 2021; 9: 638312. https://doi.org/10.3389/fcell.2021.638312
  2. Palameta S., Manrique-Rincon A.J., Toscaro J.M., Semionatto I.F., Fonseca M.C., Rosa R.S.M., Ruas L.P., Oliveira P.S.L., Bajgelman M.C. Boosting antitumor response with PSMA-targeted immunomodulatory VLPs, harboring costimulatory TNFSF ligands and GM-CSF cytokine. Mol Ther Oncolytics. 2022; 17 (24): 650-62. https://doi.org/10.1016/j.omto.2022.02.010
  3. Zizzari I.G., Filippo A.Di., Botticelli A. Circulating CD137+ T-cells correlate with improved response to Anti-PD1 immunotherapy in patients with cancerCD137+ T-cells for a successful immunotherapy. Clinical Cancer Research. 2022; 1-11. https://doi.org/10.1158/1078-0432.CCR-21-2918
  4. Legut M., Gajic Z., Guarino M. A genome-scale screen for synthetic drivers of T. cell proliferation. Nature. 2022; 603 (7902): 728-35. https://doi.org/10.1038/s41586-022-04494-7
  5. Meier S.L., Satpathy A.T., Wells D.K. Bystander T-cells in cancer immunology and therapy. Nature Cancer. 2022; 3 (2): 143-55. https://doi.org/10.1038/s43018-022-00335-8
  6. Yi L., Jin X., Wang J., Yan Z., Cheng X., Wen T., Yang B., Wang X., Che N., Liu Z., Zhang H. CD137 agonists targeting CD137-mediated negative regulation show enhanced antitumor efficacy in lung cancer. Front Immunol. 2022; 7 (13): 771809. https://doi.org/10.3389/fimmu.2022.771809
  7. Cheng H., Zong L., Kong Y., Gu Y., Yang J., Xiang Y. Emerging targets of immunotherapy in gynecologic cancer. Onco Targets Ther. 2020; 13: 11869-82. https://doi.org/10.2147/OTT.S282530
  8. Cheng L., Cheng Y., Liu W., Shen A., Zhang D. A humanized 4-1BB-targeting agonistic antibody exerts potent antitumor activity in colorectal cancer without systemic toxicity. Journal of Translation Medicine. 2022; 1: 1-21. https://doi.org/10.21203/rs.3.rs-1352893/v1
  9. Общероссийский национальный союз. Ассоциация онкологов России. Злокачественные новообразования ободочной кишки и ректосигмоидного отдела. Клинические рекомендации. 2020.
  10. Alshogran O.Y., Al-Delaimy W.K. Understanding of international committee of medical journal editor's authorship criteria among faculty members of pharmacy and other health sciences in Jordan. J. Empir Res Hum Res Ethics. 2018; 13 (3): 276 84. https://doi.org/10.1177/1556264618764575
  11. Lang T.A., Altman D.G. Basic statistical reporting for articles published in biomedical journals: Statistical analyses and methods in the published literature or the SAMPL guidelines. Int J. Nurs Stud. 2015; 52 (1): 5-9. https://doi.org/10.10Wj.ijnurstu.2014.09.006
  12. Мудров В.А. Алгоритмы статистического анализа количественных признаков в биомедицинских исследованиях с помощью пакета программ SPSS. Забайкальский медицинский вестник. 2020; 1: 140-50.
  13. Мудров В.А. Алгоритмы статистического анализа качественных признаков в биомедицинских исследованиях с помощью пакета программ SPSS. Забайкальский медицинский вестник. 2020; 1: 151-63.
  14. Мудров В.А. Алгоритмы корреляционного анализа данных в биомедицинских исследованиях с помощью пакета программ SPSS. Забайкальский медицинский вестник. 2020; 2: 169-76.
  15. Yi L., Jin X., Wang J., Yan Z., Cheng X., Wen T., Yang B., Wang X., Che N., Liu Z., Zhang H. CD137 agonists targeting CD137-mediated negative regulation show enhanced antitumor efficacy in lung cancer. Front Immunol. 2022; 7 (13): 771809. https://doi.org/10.3389/fimmu.2022.771809
  16. Kim H.D. 4-1BB delineates distinct activation status of exhausted tumor infiltrating CD8+ T. cells in hepatocellular carcinoma. Hepatology. 2020; 71 (3): 955-71.
  17. Kayukova E.V., Sholokhov L.F., Belokrinitskaya T.E., Tereshkov P.P. Checkpoint proteins in patients with precancer and cervical cancer. BioRxiv. 2021; 02.09.430409. https://doi.org/10.1101/2021.02.09.430409
  18. Ye L., Park J.J., Yang Q. A genome-scale gain-of-function CRISPR screen in CD8 T. cells identifies proline metabolism as a means to enhance CAR-T therapy. Cell Metabolism. 2022; 34 (4): 595-614.
  19. Zhou L. Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation. Nature Immunology. 2022; 23 (2): 251-61. https://doi.org/10.1038/s41590-021-01110-0
  20. Hinner M.J., Aiba R.S.B., Jaquin T.J., Berger S., Durr M.C. Tumor-localized costimulatory T-Cell engagement by the 4-1BB/HER2 bispecific antibody-anticalin fusion PRS-343. Clin. Cancer Res. 2019; 125 (19): 5878-89. https://doi.org/10.1158/1078-0432.CCR-18-3654

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