Introduction: CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in epithelial malignancies. However, whether these cells are induced as part of an ongoing anti-tumor immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown.
Methods: CD103+ TIL were quantified in a cohort of ovarian and endometrial cancer patients by immunohistochemistry. Localization of CD103+ cells and co-expression of CD103 with CD3, CD8, CD16 and FoxP3 was assessed by immunofluorescence. Further phenotyping and functional experiments of CD103+ cells was performed mainly by flow cytometry on primary tumor digests.
Summary of the Data: In this study, we first confirmed that CD103+ TIL from ovarian and uterine cancer were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis. We further demonstrate that CD103+ TIL were almost exclusively CD3+ TCRαβ+ CD8αβ+ CD4- T cells, but heterogeneously expressed T cell memory and differentiation markers. Activation of peripheral T cells in the presence of HGSC was sufficient to trigger induction of CD103 in over 90% of all CD8+ cells in a T cell receptor (TCR)- and TGFβR1-dependent manner. Finally, CD103+ TIL isolated from primary ovarian and uterine tumors showed signs of recent activation and dominantly co-expressed key immunotherapeutic targets PD-1 and CD27.
Conclusion: Our data indicate CD103+ TIL are formed as the result of an adaptive anti-tumor immune response that might be reactivated by (dual) checkpoint inhibition.
Citation Format: Hans Nijman, Fenne Komdeur, Maartje Wouters, Hagma Workel, Kim Brunekreeft, Annechien Plat, Florine Eggink, Bea Wisman, Toos Daemen, Evelien Duiker, Harry Hollema, Marco de Bruyn. CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A108.