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

Publication date: June 2016
Source:European Journal of Cancer, Volume 60
Author(s): 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
IntroductionIntraepithelial 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.MethodsCD103+ 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.ResultsCD8+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).ConclusionsBecause 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.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1UxHMEd
via IFTTT