Profound elevation of CD8+ T cells expressing the intraepithelial lymphocyte marker CD103 (αE/β7 Integrin) in high-grade serous ovarian cancer

IntroductionTumor-infiltrating CD8+ T cells are strongly associated with survival in high-grade serous ovarian cancer, but their functional phenotype remains poorly defined. The mucosal integrin CD103 (αE/β7) facilitates the infiltration of T cells into epithelial tissues, including gut and lung mucosa, solid organ allografts, and various epithelial cancers. We reasoned that CD103 might also be expressed by tumor-reactive T cells in ovarian cancer.MethodsFlow cytometry was used to assess the frequency and phenotype of CD103-expressing T cells in primary ascites fluid from 13 patients with high-grade serous ovarian cancer and 2 patients with recurrent disease.ResultsWe report that a subset of patients with advanced serous ovarian cancer have profoundly elevated frequencies of CD103-expressing CD8+ cells in ascites (between 20% and 70% of CD8+ cells in ascites were CD103+) and that CD103 expression correlated with levels of TGF-β in ascitic fluid. Conversely, CD103 was not expressed on CD4+ cells, even in those patients with very high frequencies of CD8+CD103+ cells. CD8+CD103+ cells were antigen-experienced (CD45RA−CD45RO+CD62LloCCR7−) and of an intermediate (EM2) effector memory phenotype (CD27+CD28−). TCR repertoire analysis indicated significant skewing between CD8+CD103− and CD8+CD103+ T cell subsets, suggesting the two populations contain distinct antigenic specificities. Lastly, HLA pentamer analysis revealed that one patient in the cohort harbored a high frequency of CD8+ T cells in ascites that were specific for the tumor antigen NY-ESO-1, and that ∼ 75% of these NY-ESO-1 specific CD8+ T cells were CD103+.ConclusionsCD103+ may be a marker of activated and tumor-reactive CD8+ T cells in high-grade serous ovarian cancer.