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DOI: Changes In Tumor Infiltrating Lymphocytes Of Peripheral Blood And Tissue During Chemotherapy In Patients With Gastric Cancer
Gulnoz Golibovna Khakimova , PhD, Assistant Department Of Oncology, Pediatric Oncology, Tashkent Pediatric Medical Institute; Oncologist Of The Department Of Chemotherapy Of The Republican Specialized Scientific And Practical Medical Center Of Oncology And Radiology, Uzbekistan Golib Abdulloevich Khakimov , Prof. M.D. Head Of The Department Of Oncology, Pediatric Oncology Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan; Director Of The Tashkent City Branch Of The Republican Specialized Scientific And Practical Medical Center Of Oncology And Radiology, Tashkent, Uzbekistan Shakhnoz Golibovna Khakimova , PhD, Associate Professor Department Of Oncology, Pediatric Oncology, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan Aziz Timurovich Khakimov , Assistant Department Of Oncology, Pediatric Oncology, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan Dilbar Muradovna Almuradova , PhD, Senior Preferee Department Of Oncology, Tashkent Medical Academy, Tashkent, UzbekistanAbstract
To study the state of systemic immunity and local immunity before and during chemotherapy in patients with gastric adenocarcinoma.
From 2017 to 2018 at the Tashkent city branch of the Republican specialized scientific and practical medical center of oncology and radiology 20 primary metastatic patients with gastric adenocarcinoma received chemotherapy. The sampling of biological material (peripheral blood, tumor tissue) was carried out twice (before treatment and during the first control examination, after 3 courses). The percentage of the degree of infiltration of tumor tissue by lymphocytes (CD45+CD14-TILs) was estimated by flow cytometry; T cells (CD3+CD19-TILs); B cells (CD3-CD19+TILs); NK cells (CD3-CD16+CD56+TILs); CD16 and CD8 effector cells and their cytotoxic potential (CTP) (CD16+Perforin+TILs; CD16CTPTILs), (CD8+Perforin+TILs; CD8CTPTILs); regulatory T cells - NKT cells (CD3+CD16+CD56+TILs), CD4 (CD4+CD25+CD127-TILs) and CD8 (CD8+CD11b-CD28-TILs) regulatory cells and these parameters of systemic results. The factor of a favorable prognosis for PFS in patients with metastatic gastric cancer in the peripheral blood was an increase in the number of CD8 + T-regulatory cells (5.1% - 12.1%, p = 0.019), and in tumor tissue - an increase in the perforin potential of effector CD16 cells (0.5% - 4.9%, p = 0.030) and their cytotoxic potential (13.2% - 55.7%, p = 0.011). When assessing the changes in the indices of local immunity during chemotherapy, it was noted a negative effect of an increase of T cells (22.0% - -9.7%, p = 0.012), NKT - cells (207.9% - -13.8%, p = 0.002) and CD4 + T-regulatory cells (190.7% - -25.2%, p = 0.002). In contrast, an increase in the level of effector CD16 cells during chemotherapy increases the likelihood of surviving PFS - 9 months (-69.5% - 9.1%, p = 0.013).
Indicators of local and systemic immunity serve as additional prognostic factors for gastric cancer.
Keywords
Metastatic gastric cancer, cellular immunity, local immunity, chemotherapy
References
Berezhnaya N.M. Interaction of cells of the immune system with other components of the microenvironment. Oncology. 2009; 1 (2): 86–93.
Mantovani A. et al. Tumor immunity: effector response to tumor and role of the microenvironment. Lancet 2008; 371 (9614): 771–83.
Tupitsyn N.N. Immunophenotype of breast cancer. In the book: Breast cancer. Ed. NOT. Kushlinsky, S.M. Portnoy, K.P. Laktionova. Moscow: RAMS Publishing House, 2005; from. 174-97.
Balch C., Riley L., Bae T. et al. Patterns of human tumor infiltrating lymphocytes in 120 human cancers. Arch Surg 1990; 125 (2): 200–5.
Galon J., Pages F. et al. Cancer classification using the immunoscore: a worldwide task force. J Transl Med 2012; 10: 205.
Zamarron B.F., Chen W. Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci. 2011; 7 (5): 651-658.
Ruffell B., DeNardo D.G., Affara N.I. et al. Lymphocytes in cancer development: polarization towards protumor immunity. Cytokine Growth Factor Rev. 2010; 21: 3-10.
Shen Z. Zhou S., Wang Y. et al. Higher intratumoral infiltrated Foxp3+ Treg numbers and Foxp3+/C8+ ratio are associated with adverse prognosis in resectable gastric cancer. J Cancer Res Clin. Oncol. 2010; 136:1585-1595.
Zheng X., Song X., Shao Y. et al. Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: A meta-analysis. Oncotarget. 2017; 8. 10.18632/oncotarget.18065.
He, Q. Impact of the immune cell population in peripheral blood on response and survival in patients receiving neoadjuvant chemotherapy for advanced gastric cancer / Q. He, G. Li, X. Ji et al.// Tumor Biology. – 2017. – Vol.39, N5. – е.101042831769757.
Zabotina, T.N. Features of the subpopulation composition of peripheral blood lymphocytes and infiltrating the tumor in patients with squamous cell carcinoma of the head and neck / T.N. Zabotina, A.I. Chertkova, V.T. Tsiklauri et al. // Immunology. - 2019. - T.40, No. 3. - S. 10-19.
Loi, S. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy / S. Loi et al. // J Clin Oncol. – 2013. – Vol.31. – Р. 860-7.
Murta, E.F. Lymphocyte subpopulations in patients with advanced breast cancer submitted to neoadjuvant chemotherapy / E.F. Murta, J.M. de Andrade et al. // Tumori. – 2000. – Vol.86, N5. – Р. 403-7.
Chang, W.C. Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma / W.C. Chang, C.H. Li, S.C. Huang et al. // Cancer. – 2010. – Vol.116. – Р. 5777-5788.
Gao, Q. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection / Q. Gao, S.J. Qiu, J. Fan et al. // J Clin Oncol. – 2007. – Vol.25. – Р. 2586-2593.
Ormandy, L.A. Increased populations of regulatory T-cells in peripheral blood of patients with hepatocellular carcinoma / L.A. Ormandy, T. Hillemann, H. Wedemeyer et al. // Cancer Res. – 2005. – Vol.65. – Р. 2457-2464.
Wu, Y. Clinical significance of peripheral blood and tumor tissue lymphocyte subsets in cervical cancer patients / Y. Wu, S. Ye, S. Goswami et al. / BMC Cancer. – 2020. – Vol.20, N1. – Р. 173.
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