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Clin Cancer Res. 2014 Jan 15;20(2):434-44. doi: 10.1158/1078-0432.CCR-13-1877. Epub 2013 Nov 4.

Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer.

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1
Authors' Affiliations: Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency; Department of Biochemistry and Microbiology, University of Victoria; Departments of Pathology and Laboratory Medicine and Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

BACKGROUND:

The presence of CD8(+) tumor-infiltrating lymphocytes (TIL) is associated with prolonged survival in high-grade serous ovarian cancer (HGSC) and other epithelial cancers. Survival is most strongly associated with intraepithelial versus intrastromal CD8(+) TILs; however, the mechanisms that promote the intraepithelial localization of TILs remain poorly understood. We hypothesized that intraepithelial CD8(+) TILs, like normal mucosal intraepithelial lymphocytes, might express CD103, a subunit of αE/β7 integrin, which binds E-cadherin on epithelial cells.

METHODS:

A large collection of primary ovarian tumors (HGSC, endometrioid, mucinous, and clear cell) was analyzed by immunohistochemistry for the presence of TIL-expressing CD103. The activation and differentiation status of CD103(+) TILs were assessed by flow cytometry. The prognostic significance of TIL subsets was evaluated by Kaplan-Meier analysis.

RESULTS:

CD103(+) TILs were present in all major ovarian cancer subtypes and were most abundant in HGSC. CD103(+) TILs were preferentially localized to epithelial regions of tumors and were comprised predominantly of CD8(+) T cells expressing activation (HLA-DR, Ki-67, PD-1) and cytolytic (TIA-1) markers, as well as CD56(+) NK cells. Tumor infiltration by CD103(+) TILs was strongly associated with patient survival in HGSC. Tumors containing CD8(+) TILs that were CD103(-) showed poor prognosis equivalent to tumors lacking CD8(+) TILs altogether.

CONCLUSIONS:

CD103(+) TILs comprise intraepithelial, activated CD8(+) T cells, and NK cells and are strongly associated with patient survival in HGSC. CD103 may serve as a useful marker for enriching the most beneficial subsets of TILs for immunotherapy.

PMID:
24190978
DOI:
10.1158/1078-0432.CCR-13-1877
[Indexed for MEDLINE]
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