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Clin Cancer Res. 2012 Jun 15;18(12):3281-92. doi: 10.1158/1078-0432.CCR-12-0234. Epub 2012 May 2.

CD20+ tumor-infiltrating lymphocytes have an atypical CD27- memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer.

Author information

  • 1Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada. jnielsen@bccancer.bc.ca

Abstract

PURPOSE:

Tumor-infiltrating lymphocytes (TIL), in particular CD8(+) T cells and CD20(+) B cells, are strongly associated with survival in ovarian cancer and other carcinomas. Although CD8(+) TIL can mediate direct cytolytic activity against tumors, the role of CD20(+) TIL is poorly understood. Here, we investigate the possible contributions of CD20(+) TIL to humoral and cellular tumor immunity.

EXPERIMENTAL DESIGN:

Tumor and serum specimens were obtained from patients with high-grade serous ovarian cancer. CD8(+) and CD20(+) TIL were analyzed by immunohistochemistry and flow cytometry. Immunoglobulin molecules were evaluated by DNA sequencing. Serum autoantibody responses to the tumor antigens p53 and NY-ESO-1 were measured by ELISA.

RESULTS:

The vast majority of CD20(+) TIL were antigen experienced, as evidenced by class-switching, somatic hypermutation, and oligoclonality, yet they failed to express the canonical memory marker CD27. CD20(+) TIL showed no correlation with serum autoantibodies to p53 or NY-ESO-1. Instead, they colocalized with activated CD8(+) TIL and expressed markers of antigen presentation, including MHC class I, MHC class II, CD40, CD80, and CD86. The presence of both CD20(+) and CD8(+) TIL correlated with increased patient survival compared with CD8(+) TIL alone.

CONCLUSIONS:

In high-grade serous ovarian tumors, CD20(+) TIL have an antigen-experienced but atypical CD27(-) memory B-cell phenotype. They are uncoupled from serum autoantibodies, express markers of antigen-presenting cells, and colocalize with CD8(+) T cells. We propose that the association between CD20(+) TIL and patient survival may reflect a supportive role in cytolytic immune responses.

Comment in

PMID:
22553348
DOI:
10.1158/1078-0432.CCR-12-0234
[PubMed - indexed for MEDLINE]
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