Doktor axborotnomasi 2025, № (117)

Тема статьи

IMMUNOLOGICAL FACTORS IN OVARIAN CANCER METASTASIS (183-189)

Авторы

F. G. Ulmasov, I. R. Minnullin, B. S. Esankulova, B. A. Davronov

Учреждение

Samarkand state medical university, Samarkand, Uzbekistan

Аннотация

Epithelial ovarian cancer (EOC) remains a leading cause of mortality among gynecological malignancies due to its metastatic nature and late-stage diagnosis. This review focuses on the role of the immune system in ovarian can cer metastasis and progression. The interplay between tumor cells and the immune system is multifaceted, involving both immune surveillance and tumor-mediated immunosuppression. Tumor-associated immune cells, including regu latory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells, contribute to an immunosuppres sive microenvironment that supports tumor growth and dissemination. Immunotherapy, particularly checkpoint inhibi tors targeting PD-1/PD-L1 and CTLA-4 pathways has shown potential, but remains limited in efficacy. The review emphasizes the need for biomarker development and combination therapies to enhance patient outcomes. Understand ing the immunological mechanisms underlying ovarian cancer metastasis is critical for advancing therapeutic strate gies.

Ключевые слова

Epithelial Ovarian Cancer (EOC), Immunotherapy, Tumor Microenvironment (TME), Immune Surveil lance, Checkpoint Inhibitors, Immunosuppressive Mechanisms, Ovarian Cancer Metastasis.

Литературы

1. Ben Arie A., McNally L., Kapp D.S., Teng N.N. The omentum and omentectomy in epithelial ovarian cancer: a reappraisal. Part I. Omental function and history of omentectomy. Gynecol Oncol. 2013;131(3):780–3. DOI: 10.1016/j.ygyno.2013.09.014 2. Arie A.B., McNally L., Kapp D.S., Teng N.N. The omentum and omen tectomy in epithelial ovarian cancer: a reappraisal. Part II. The role of omentectomy in the staging and treatment of apparent early stage epithelial ovarian cancer. Gynecol Oncol. 2013;131(3):784–90. DOI: 10.1016/j.ygyno.2013.09.013 3. McNally L., Teng N.N., Kapp D.S., Karam A. Does omentectomy in epithelial ovarian cancer affect survival? An analysis of the Surveil lance, Epidemiology, and End Results database. Int J Gynecol Cancer. 2015;25(4):607–15. DOI: 10.1097/IGC.0000000000000412 4. Bahar S.G., Rokkam V.R. Omentum Tumors. [Updated 2020 Oct 10]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563226/ 5. Havrlentova L., Faistova H., Mazur M., Ziak D., Polak S. Comparative analysis of human omental milky spots between the patients with colon cancer and the control group. Bratisl Lek Listy. 2017;118(10):580–4. DOI: 10.4149/BLL_2017_111 6. Cipolletta D., Cohen P., Spiegelman B.M., Benoist C., Mathis D. Ap pearance and disappearance of the mRNA signature characteristic of Treg cells in visceral adipose tissue: age, diet, and PPARγ effects. Proc Natl Acad Sci USA. 2015;112(2):482–7. DOI: 10.1073/pnas.1423486112 7. Ke X., Shen L. Targeting cytokines secreted by CD4+ CD25high CD127low regulatory T cells inhibits ovarian cancer progression. Scand J Immu nol. 2019;89(2):e12736. DOI: 10.1111/sji.12736 8. Krishnan V., Tallapragada S., Schaar B., Kamat K., Chanana A.M., Zhang Y., et al. Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1. Com mun Biol. 2020;3 (1):524. DOI: 10.1038/s42003-020-01246-z 9. Etzerodt A., Moulin M., Doktor T.K., Delfini M., Mossadegh-Keller N., Bajenoff M., et al. Tissue-resident macro phages in omentum promote metastatic spread of ovarian cancer. J Exp Med. 2020;217(4):e20191869. DOI: 10.1084/jem.20191869 10. Lee W., Ko S.Y., Mohamed M.S., Kenny H.A., Lengyel E., Naora H. Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum. J Exp Med. 2019;216(1):176–94. DOI: 10.1084/ jem.20181170 11. Zhang Q., Zhou W., Yu S., Ju Y., Kit Yan To S., Sze Tsai Wong A., et al. Metabolic reprogramming of ovarian cancer involves ACSL1-mediated metastasis stimulation through upregulated protein myristoylation. Oncogene. 2021;40:97–111. DOI: 10.1038/s41388-020-01516-4 12. Nieman K.M., Kenny H.A., Penicka C.V., Ladanyi A., Buell-Gut brod R., Zillhardt M.R., et al. Adipocytes pro mote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17(11):1498–503. DOI: 10.1038/nm.2492 13. Ladanyi A., Mukherjee A., Kenny H.A., Johnson A., Mitra A.K., Sun daresan S., et al. Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis. Oncogene. 2018;37(17):2285–301. DOI: 10.1038/ s41388-017-0093-z 14. Hu J., Liu Z., Wang X. Does TP53 mutation promote ovarian cancer metastasis to omentum by regulating lipid metabolism. Med Hypoth eses. 2013;81(4):515–20. DOI: 10.1016/j.mehy.2013.06.009 15. Cole A.J., Dwight T., Gill A.J., Dickson K.-A., Zhu Y., Clarkson A., et al. Assessing mutant p53 in primary high grade serous ovarian cancer using immunohistochamistry and massively parallel sequencing. Sci Rep. 2016;6:26191. DOI: 10.1038/srep26191 16. McKenzie A.J., Hicks S.R., Svec K.V., Naughton H., Edmunds Z.L., Howe A.K. The mechanical microenviron ment regulates ovarian can cer cell morphology, migration, and spheroid disaggregation. Sci Rep. 2018;8(1):7228. DOI: 10.1038/s41598-018-25589-0 17. OH Ubaydullayevna, EB Sobirovna, SN Yusupovna //THE OPTIMIZATION OF EARLY DIAGNOSIS OF CERVICAL CANCER AND ITS RECURRENCES - Conferencea, 2023 18. OH Ubaydullayevna, EB Sobirovna, MM Bakhtiyorovich//PREDICTION AND STUDY OF THE OCCUR RENCE OF CERVICAL CANCER RECURRENCE International Journal of Medical Sciences And Clinical Re search 3 (04), 121-124 19. Esankulova Bustonoy Sobirovna, Ulmasov Firdavs Gayratovich//ANALYSIS OF THE TUMOR MICROENVI RONMENT OF OVARIAN TUMORS USING IMMUNOHISTOCHEMISTRY// Биология ва тиббиёт муаммо лари 2024, №5 (156) 20. Ulmasov F.G., Esankulova B.S. mmunohistochemical study of the ovarian cancer microenvironment at different stages: the role of immune cells in tumor progression // Journal of Biomedicine and Practice. 2024, vol. 9, issue 5, pp. 21. Winiarski B.K., Cope N., Alexander M., Pilling L.C., Warren S., Ache son N., et al. Clinical relevance of in creased endothelial and mesothe lial expression of proangiogenic proteases and VEGFA in the omentum of pa tients with metastatic ovarian high-grade serous carcinoma. Transl Oncol. 2014;7(2):267–76.e4. DOI: 10.1016/ j.tranon.2014.02.013 22. Wang H., Huang X., Zhang J., Shao N., Chen L.O., Ma D., et al. The expression of VEGF and Dll4/Notch path way molecules in ovarian can cer. Clin Chim Acta. 2014;436:243–8. DOI: 10.1016/j.cca.2014.06.005 23. Sopo M., Anttila M., Hämäläinen K., Kivelä A., Ylä-Herttuala S., Kos ma V.M., et al. Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer. BMC Cancer. 2019;19(1):584. DOI: 10.1186/ s12885-019-5757-3 24. Roggiani F., Mezzanzanica D., Rea K., Tomassetti A. Guidance of sig naling activations by cadherins and integ rins in epithelial ovarian can cer cells. Int J Mol Sci. 2016;17(9):1387. DOI: 10.3390/ijms17091387 25. Mui K.L., Chen C.S., Assoian R.K. The mechanical regulation of integrin-cadherin crosstalk organizes cells, sig naling and forces. J Cell Sci. 2016;129(6):1093–100. DOI: 10.1242/jcs.183699 26. Makrilia N., Kollias A., Manolopoulos L., Syrigos K. Cell adhesion molecules: role and clinical significance in cancer. Cancer Invest. 2009;27(10):1023–37. DOI: 10.3109/07357900902769749 27. Yi Y., Cheng J.C., Klausen C., Leung P.C.K. Activin A promotes ovarian cancer cell migration by suppressing E cadherin expression. Exp Cell Res. 2019;382(2):111471. DOI: 10.1016/j.yexcr.2019.06.016 28. Janiszewska M., Primi M.C., Izard T. Cell adhesion in cancer: Beyond the migration of single cells. J Biol Chem. 2020;295(8):2495–05. DOI: 10.1074/jbc.REV119.007759 38 29. Wong C.W., Dye D.E., Coombe D.R. The role of immunoglobulin su perfamily cell adhesion molecules in cancer metastasis. Int J Cell Biol. 2012; 2012:340296. DOI: 10.1155/2012/340296 30. Borsig L. Selectins in cancer immunity. Glycobiology. 2018;28(9):648 55. DOI: 10.1093/glycob/cwx105