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

Hagma H. Workel, Fenne L. Komdeur, Maartje C. A. Wouters, Annechien Plat, Harry G. Klip, Florine A. Eggink, G. Bea A. Wisman, Henriette J. G. Arts, Maaike H. M. Oonk, Marian J. E. Mourits, Refika Yigit, Marco Versluis, Evelien W. Duiker, Harry Hollema, Marco de Bruyn, Hans W. Nijman*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

105 Citaten (Scopus)


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 alpha E subunit of the alpha Eb7integrin, 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. (C) 2016 Elsevier Ltd. All rights reserved.

Originele taal-2English
Pagina's (van-tot)1-11
Aantal pagina's11
TijdschriftEuropean Journal of Cancer
StatusPublished - jun.-2016

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