CD103+intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCR alpha beta+CD8 alpha beta plus T cells that can be targeted for cancer immunotherapy

作者：Komdeur Fenne L; Wouters Maartje C A; Workel Hagma H; Tijans Aline M; Terwindt Anouk L J; Brunekreeft Kim L; Plat Annechien; Klip Harry G; Eggink Florine A; Leffers Ninke; Helfrich Wijnand; Samplonius Douwe F; Bremer Edwin; Wisman G Bea A; Daemen Toos; Duiker Evelien W; Hollema Harry; Nijman Hans W^*; de Bruyn Marco

来源：Oncotarget, 2016, 7(46): 75130-75144.

DOI：10.18632/oncotarget.12077

• tumor-infiltrating lymphocytes
• high-grade serous ovarian cancer
• CD103
• TGF-beta
• cancer immunotherapy

CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC 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+ TCR alpha beta+ CD8 alpha beta+ 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 TGF beta R1-dependent manner. Finally, CD103+ TIL isolated from primary HGSC showed signs of recent activation and dominantly co-expressed key immunotherapeutic targets PD-1 and CD27. Taken together, our data indicate CD103+ TIL in HGSC are formed as the result of an adaptive anti-tumor immune response that might be reactivated by (dual) checkpoint inhibition.

• 出版日期2016-11-15