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CD103 defines intraepithelial CD8+ PD1+ tumour-infiltrating lymphocytes of prognostic significance in endometrial adenocarcinoma

Published:March 31, 2016DOI:https://doi.org/10.1016/j.ejca.2016.02.026

      Highlights

      • CD103 is a marker for intraepithelial CD8+ T-cells in endometrial carcinoma (EC).
      • The presence of CD103+ T-cells is associated with improved survival in EC.
      • CD8+CD103+ T-cells are antigen-experienced and widely express PD1.
      • The potential of CD103 as a population for adoptive transfer immunotherapy should be investigated further.

      Abstract

      Introduction

      Intraepithelial CD8+ tumour-infiltrating T-lymphocytes (TIL) are associated with a prolonged survival in endometrial cancer (EC). By contrast, stromal infiltration of CD8+ TIL does not confer prognostic benefit. A single marker to discriminate these populations would therefore be of interest for rapid assessment of the tumour immune contexture, ex vivo analysis of intraepithelial and stromal T-cells on a functional level and/or adoptive T-cell transfer. Here we determined whether CD103, the αE subunit of the αEβ7integrin, can be used to specifically discriminate the epithelial and stromal CD8+ TIL populations in EC.

      Methods

      CD103+ TIL were quantified in a cohort of 305 EC patients by immunohistochemistry. Localization of CD103+ cells and co-expression of CD103 with CD3, CD8, CD16 and FoxP3 were assessed by immunofluorescence. Further phenotyping of CD103+ cells was performed by flow cytometry on primary endometrial tumour digests.

      Results

      CD8+CD103+ cells were preferentially located in endometrial tumour epithelium, whereas CD8+CD103− cells were located in stroma. CD103+ lymphocytes were predominantly CD3+CD8+ T-cells and expressed PD1. The presence of a high CD103+ cell infiltration was associated with an improved prognosis in patients with endometrial adenocarcinoma (p = 0.035). Moreover, this beneficial effect was particularly evident in high-risk adenocarcinoma patients (p = 0.031).

      Conclusions

      Because of the restricted expression on intraepithelial CD8+ T-cells, CD103 may be a suitable biomarker for rapid assessment of immune infiltration of epithelial cancers. Furthermore, this intraepithelial tumour-reactive subset might be an interesting T-cell subset for adoptive T-cell transfer and/or target for checkpoint inhibition therapy.

      Keywords

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