CD20+ Tumor-Infiltrating Lymphocytes Have an Atypical CD27− Memory Phenotype and Together with CD8+ T Cells Promote Favorable Prognosis in Ovarian Cancer

Abstract

Purpose: Tumor-infiltrating lymphocytes (TIL), in particular CD8þ T cells and CD20 þ B cells, are strongly associated with survival in ovarian cancer and other carcinomas. Although CD8 þ TIL can mediate direct cytolytic activity against tumors, the role of CD20 þ TIL is poorly understood. Here, we investigate the possible contributions of CD20 þ TIL to humoral and cellular tumor immunity.Experimental Design: Tumor and serum specimens were obtained from patients with high-grade serous ovarian cancer. CD8þ and CD20 þ 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 þ TIL were antigen experienced, as evidenced by class-switching, somatic hypermutation, and oligoclonality, yet they failed to express the canonical memory marker CD27. CD20 þ TIL showed no correlation with serum autoantibodies to p53 or NY-ESO-1. Instead, they colocalized with activated CD8 þ TIL and expressed markers of antigen presentation, including MHC class I, MHC class II, CD40, CD80, and CD86. The presence of both CD20 þ and CD8 þ TIL correlated with increased patient survival compared with CD8 þ TIL alone. Conclusions:In high-grade serous ovarian tumors, CD20 þ TIL have an antigen-experienced but atypical CD27 À memory B-cell phenotype. They are uncoupled from serum autoantibodies, express markers of antigen-presenting cells, and colocalize with CD8 þ T cells. We propose that the association between CD20 þ TIL and patient survival may reflect a supportive role in cytolytic immune responses.

Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients

“…CD20 C B cells contribute both to humoral immunity as antibody-producing cells, but also to cellular immunity by serving as antigen-presenting cells (APCs) and/or by providing costimulatory signals to T cells. 19,20 A favorable effect of tumor-infiltrating B cells on patient prognosis was previously reported in cutaneous melanoma, 21 breast cancer 22 and ovarian cancer, 23 but the mechanism linking the accumulation of these cells in the tumor microenvironment and better prognosis remains poorly understood. Nielsen et al found that tumor-infiltrating B cells expressed markers of antigen presentation and could have a function of professional APCs to support the T cell-mediated immune anticancer response.…”

“…Nielsen et al found that tumor-infiltrating B cells expressed markers of antigen presentation and could have a function of professional APCs to support the T cell-mediated immune anticancer response. 23 Another report underlines the capacity of B cells found in TLS to produce antibodies that specifically recognize tumor antigens. 24 In our series, we hypothesize that the anticancer effect of T-bet C T cells and CD20 C B cells could be balanced by the immunosuppressive action of Foxp3 C Tregs since a high intratumoral density of these particular immune cells are significantly associated with reduced RFS.…”

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

“…A randomized clinical trial involving more than 1000 patients revealed that, in patients receiving neoadjuvant chemotherapy, the broad infiltration of lymphocytes into tumors seemed to be more clinically beneficial than no lymphocytic infiltration, in terms of achieving a pathologic complete response after chemotherapy 54 . In conclusion, this study shows that elevated PLR is closely associated with poor survival outcome in patients with OC.…”

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

“…In this context, it is therefore surprising that ELFs arise in tumours at all. However, ELFs have been described in numerous cancers including colorectal,60, 88 rectal,89 breast,67, 90, 91 ovarian67, 92 and germ cell93 cancers, as well as melanoma,62, 67, 94 mucosal‐associated lymphoid tissue lymphoma39 and non‐small cell lung carcinoma95, 96 (NSCLC; see Dieu‐Nosjean et al . for a comprehensive review of ELFs in cancer9).…”