Pro- and anti-tumour effects of B cells and antibodies in cancer: a comparison of clinical studies and preclinical models

Abstract

The primary immune role of B cells is to produce antibodies, but they can also influence T cell function via antigen presentation and, in some contexts, immune regulation. Whether their roles in tumour immunity are similar to those in other chronic immune responses such as autoimmunity and chronic infection, where both pro- and anti-inflammatory roles have been described, remains controversial. Many studies have aimed to define the role of B cells in antitumor immune responses, but despite this considerable body of work, it is not yet possible to predict how they will affect immunity to any given tumour. In many human cancers, the presence of tumour-infiltrating B cells and tumour-reactive antibodies correlates with extended patient survival, and this clinical observation is supported by data from some animal models. On the other hand, T cell responses can be adversely affected by B cell production of immunoregulatory cytokines, a phenomenon that has been demonstrated in humans and in animal models. The isotype and concentration of tumour-reactive antibodies may also influence tumour progression. Recruitment of B cells into tumours may directly reflect the subtype and strength of the anti-tumour T cell response. As the response becomes chronic, B cells may attenuate T cell responses in an attempt to decrease host damage, similar to their described role in chronic infection and autoimmunity. Understanding how B cell responses in cancer are related to the effectiveness of the overall anti-tumour response is likely to aid in the development of new therapeutic interventions against cancer.

CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

“…Tumor-promoting activities by B cells have been commonly described in animal models (41), whereas most human studies associate B-TIL with positive cancer outcomes (42)(43)(44). The latter include dependence on a B-TIL presence for the prognostic value of CD8 + TIL (45), increased CD4 + TIL clonality linked with high B-TIL density (46), and evidence of Ag recognition, somatic hypermutation, and oligoclonality in B-TIL (45).…”

“…Their persistence in the immunosuppressive tumor microenvironment could explain their ability to attract and guide B-TIL migration through the tumor. Thus, late participation by B-TIL in tumor immunity may be more effective for the generation of antitumor responses (44).…”

Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non–Small Cell Lung Cancer Patients

“…Further, approximately 50% of patient samples tested have antibody reactivity to tumor antigens (19). It has also been suggested in murine models that TIL-Bs generate antitumor cytokines, directly kill tumor cells, and present tumor antigens (24–31). Antigen presentation is an important function of B cells.…”

“…Activated B cells from control donor peripheral blood lymphocytes (PBL) present antigens to CD4 + and CD8 + T cells (27,29). Autoimmunity and allograft rejection studies describe the importance of B cells in the formation of TLS and in presentation of auto- or allo-antigens that ultimately influence the CD4 + T-cell phenotype (25, 29–31). TIL-Bs may also present antigens more effectively than tumor dendritic cells (DCs), due to selective presentation of cognate antigen through surface Ig molecules.…”

A Paradoxical Correlation of Cancer-Associated Fibroblasts With Survival Outcomes in B-Cell Lymphomas and Carcinomas

“…It is unclear if activated CAFs in carcinomas are also associated with immunosuppressive populations of B cells due to poorly defined markers for such cells (Sarvaria et al, 2017). Moreover, studies investigating the associations of B cell subsets with tumor progression using defined B-cell markers have produced conflicting results even within the same tumor type (Guy et al, 2016). An insufficient understanding of the roles of B cells in carcinomas has hindered the development of rational clinical trials targeting B-cells in carcinomas.…”