2020, Number 4
Correlation of the lymphocytary immunophenotype in blood, ascites and tumoral tissue in patients with ovarian cancer
Language: Spanish
References: 35
Page: 1-23
PDF size: 615.34 Kb.
ABSTRACT
Introduction: Ovarian cancer with epithelial origin is the most lethal of all gynecological cancers. The lymphocytary infiltrate in the tumor, the ascites and the blood are associated with the survival and the therapeutic response.Objective: Assess the correlation of the lymphocytary composition between blood, ascites and tissue of the tumor in patients with ovarian cancer of epithelial origin.
Methods: It was conducted an analytical cross-sectional study in the National Institute of Oncology and Radiobiology (INOR, by its acronym in Spanish), in Havana, Cuba during 2017. 33 samples of blood, ascites and ovaric tumoral tissue were studied through a panel of multiparameters flow cytometry, and in addition were studied blood samples of 35 supposedly healthy women. It was assesed the composition and correlation among lymphocytary immunophenotypes.
Results: There were found changes in the lymphocytary immunophenotype in the blood of patients in comparison with the controls. The concentration of NK cells was found significantly high, with 12,5% and 15,8% in controls and patients, respectively. The variance analysis showed that the variability of the lymphocytes concentrations between blood, ascites and ovaric tissue was not by chance. The population of ciytotoxic lymphocytes, T regulators, NKT and activated cells described an increasing trend in the blood, the ascites and the tissue; while the NK, the B lymphocytes and the helper cells showed an opposite trend. The activated immunophenotypes of T regulators and the cytotoxic lymphocytes had an inverse correlation in ascites and tumoral tissue with R2: 0,70 and 0,45, respectively.
Conclusions: It was evidenced the increase of cells with cytotoxic function and T regulators in the tissue and the ascites with T regulators lymphocytes. The correlation found in some homologous immunophenotypes among sections suggests that can be estimated cells concentrations from the blood. The relation among functional phenotypes showed a supressor environment, independently from the global concentrations of CD8 and T regulators.
REFERENCES
Lukesova S, Vroblova2 V, Tosner J, Kopecky J, Sedlakova I, Čermáková E, et al. Comparative study of various subpopulations of cytotoxic cells in blood and ascites from patients with ovarian carcinoma. Contemp Oncol (Pozn) [Internet]. 2015 [acceso 12/01/2019];19(4):290-9. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631306/
Zhang W, Liu K, Ye B, Hu G, Zhao K, Ren Y. Clinical and biological effects of tumor‑associated lymphocytes in the presence or absence of chemotherapy for malignant ascites in ovarian cancer patients. Oncol Let [Internet]. 2017 [acceso 12/01/2019];14:3379-86. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587970/
Muñoz-Galván S, Felipe-Abrio B, García-Carrasco M, Domínguez-Piñol J, Suarez-Martinez E, Verdugo-Sivianes EM, et al. New markers for human ovarian cancer that link platinum resistance to the cancer stem cell phenotype and define new therapeutic combinations and diagnostic tools. J Exp Clin Cancer Res [Internet]. 2019 [acceso 12/01/2019];38(1):234. Disponible en: https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1245-5
Owens GL, Price MJ, Cheadle EJ, Hawkins RE, Gilham DE, Edmondson RJ. Ex vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells. Cancer Immunol Immunother [Internet]. 2018 [acceso 12/01/2019];67:1519-31. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182400/
Rådestad E, Klynning C, Stikvoort A, Mogensen O, Nava S, Magalhaes I, et al. Immune profiling and identification of prognostic immune-related risk factors in human ovarian cancer, OncoImmunology [Internet]. 2019 [acceso 12/01/2019];8(2):e1535730. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343785/
Goode EL, Block MS, Kalli KR, Vierkant RA, Chen W, Fogarty ZC, et al. Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer. JAMA Oncol [Internet]. 2017 [acceso 12/01/2019];3(12):1-9. Disponible en: https://jamanetwork.com/journals/jamaoncology/fullarticle/2657136
Pignon JC, Jegede O, Shukla SA, Braun DA, Horak CE, Wind-Rotolo M, et al. irRECIST for the Evaluation of Candidate Biomarkers of Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma: Analysis of a Phase II Prospective Clinical Trial. Clin Cancer Res [Internet]. 2019 [acceso 12/01/2019];25(7):2174-84. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30670497/
Jang M, Poh-Yin Y, Hasegawa K, Ikeda Y, Fujiwara K, Fleming GF, et al. Characterization of T cell repertoire of blood, tumor, and ascites in ovarian cancer patients using next generation sequencing. Oncoimmunol [Internet]. 2015 [acceso 12/01/2019];4(11):1-10. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589054/
Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med [Internet]. 2004 [acceso 12/01/2019];10(9):942-9. Disponible en: https://pubmed.ncbi.nlm.nih.gov/15322536/
Jiménez-Sánchez A, Memon D, Pourpe S, Veeraraghavan H, Li Y, Vargas HA, et al. Heterogeneous tumor-immune microenvironments among differentially growing metastases in an ovarian cancer patient. Cell [Internet]. 2017 [acceso 12/01/2019];170:927-38. Disponible en: https://pubmed.ncbi.nlm.nih.gov/28841418/
Kovacsovics-Banlowski M, Chisholm L, Vercellini J, Tucker CG, Montler R, Haley D, et al. Detailed characterization of tumor infiltrating lymphocytes in two distinct human solid malignancies show phenotypic similarities. J ImmunoTher Cancer [Internet]. 2014 [acceso 12/01/2019];2(1):38. Disponible en: https://pubmed.ncbi.nlm.nih.gov/25436113/
Savant SS, Sriramkumar S, O’Hagan HM. The role of inflammation and inflammatory mediators in the development, progression, metastasis, and chemoresistance of epithelial ovarian cancer. Cancer [Internet]. 2018 [acceso 12/01/2019];10(8):251. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116184/
Kroeger DR, Milne K, Nelson BH. Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer. Clin Cancer Res [Internet]. 2016 [acceso 12/01/2019];22(12):3005-15. Disponible en: https://pubmed.ncbi.nlm.nih.gov/26763251/
Matsuzaki J, Tsuji T, Chodon T, Ryan C, Koya RC, Odunsi K. A rare population of tumor antigen-specific CD4+CD8+ double-positive αβ T lymphocytes uniquely provide CD8-independent TCR genes for engineering therapeutic T cells. J Immunother Cancer [Internet]. 2019 [acceso 12/01/2019];7:1-18. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325755/
Liang H, Chu X, Zhao J, Xing G, Si Y. Elevated peripheral blood B lymphocytes and CD3+CD4‑CD8‑ T lymphocytes in patients with non‑small cell lung cancer: A preliminary study on peripheral immune profile. Oncolol Lett [Internet]. 2018 [acceso 12/01/2019];15:8387-95. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5950528/
Wefers C, Duiveman-de Boer T, Yigit R, Zusterzeel PLM, van Altena AM, Massuger LFAG, et al. Survival of Ovarian Cancer Patients Is Independent of the Presence of DC and T Cell Subsets in Ascites. Front Immunol [Internet]. 2019 [acceso 12/01/2019];9:3156. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336918/
Wicherek L, Jozwicki W, Windorbska W, Roszkowski K, Lukaszewska E, Wisniewski M, et al. Analysis of Treg Cell Population Alterations in the Peripheral Blood of Patients Treated Surgically for Ovarian Cancer. A Preliminary Report. Am J Reprod Immunol. 2011;66:444-50. DOI: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0897.2011.01024.x
Bonertz A, Weitz J, Pietsch DH, Rahbari NN, Schlude C, Ge Y, Juenger S, Vlodavsky I, Khazaie K, Jaeger D, et al. Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. J Clin Invest [Internet]. 2009 [acceso 12/01/2019];119:3311-21. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769188/