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CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

Komdeur, F. L., Wouters, M. C. A., Workel, H. H., Tijans, A. M., Terwindt, A. L. J., Brunekreeft, K. L., Plat, A., Klip, H. G., Eggink, F. A., Leffers, N., Helfrich, W., Samplonius, D. F., Bremer, E., Wisman, G. B. A., Daemen, T., Duiker, E. W., Hollema, H., Nijman, H. W. & de Bruyn, M., 15-Nov-2016, In : Oncotarget. 7, 46, p. 75130-75144 15 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)75130-75144
Number of pages15
JournalOncotarget
Volume7
Issue number46
Publication statusPublished - 15-Nov-2016

    Keywords

  • tumor-infiltrating lymphocytes, high-grade serous ovarian cancer, CD103, TGF-beta, cancer immunotherapy, TUMOR-INFILTRATING LYMPHOCYTES, LYTIC GRANULE POLARIZATION, PROGNOSTIC-SIGNIFICANCE, ADOPTIVE IMMUNOTHERAPY, FAVORABLE PROGNOSIS, CD103 EXPRESSION, TGF-BETA, CARCINOMA, PROMOTES, LUNG

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