Blocking of EphA2 on Endometrial Tumor Cells Reduces Susceptibility to Vδ1 Gamma-Delta T-Cell-Mediated Killing

• Published in: Frontiers in immunology 2021-10, Vol.12, p.752646-752646
• Main Authors: Hudecek, Robert, Kohlova, Barbora, Siskova, Ingrid, Piskacek, Martin, Knight, Andrea
• Format: Article
• Language: English
• Subjects: Adult; Cell Line, Tumor; cytotoxicity; Endometrial Neoplasms - immunology; Endometrial Neoplasms - metabolism; endometriosis; Endometriosis - immunology; Endometriosis - metabolism; Female; gamma-delta T cells; Humans; Immunology; innate immunity; Intraepithelial Lymphocytes - immunology; Middle Aged; peritoneal fluid; Receptor, EphA2 - metabolism; tyrosine kinase EphA2
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.752646

Endometriosis is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus causing chronic inflammation, severe pain, and infertility. However, the innate immunity of gamma-delta (γδ) T lymphocytes in endometriosis has not been characterized. Women with endometriosis present numerous endocrine and immune dysfunctions and elevated risk for endometrial, ovarian, and breast cancers. The tyrosine kinase EphA2 is often overexpressed in cancer including endometrial carcinoma. We analyzed Vδ1 and Vδ2 γδ T cells in peripheral blood and paired peritoneal fluid samples in endometriosis patients (  = 19) and compared the counts with that of age- and sex-matched healthy donors (  = 33) using flow cytometry. Vδ1 and Vδ2 T cells isolated from healthy donors were used against KLE, RL-95, and Ishikawa endometrial tumor cells in 4 h flow cytometric cytotoxicity assays. The EphA2 blocking studies were performed using antibody, small-molecule inhibitor ALW-II-41-27, and the CRISPR/Cas9. We determined Vδ1 T cells substantially reduced in patients' peripheral blood (