Emerging concepts regarding pro- and anti tumor properties of B cells in tumor immunity

Abstract

Controversial views regarding the roles of B cells in tumor immunity have existed for several decades. However, more recent studies have focused on its positive properties in antitumor immunity. Many studies have demonstrated a close association of the higher density of intratumoral B cells with favorable outcomes in cancer patients. B cells can interact with T cells as well as follicular dendritic cells within tertiary lymphoid structures, where they undergo a series of biological events, including clonal expansion, somatic hypermutation, class switching, and tumor-specific antibody production, which may trigger antitumor humoral responses. After activation, B cells can function as effector cells via direct tumor-killing, antigen-presenting activity, and production of tumor-specific antibodies. At the other extreme, B cells can obtain inhibitory functions by relevant stimuli, converting to regulatory B cells, which serve as an immunosuppressive arm to tumor immunity. Here we summarize our current understanding of the bipolar properties of B cells within the tumor immune microenvironment and propose potential B cell-based immunotherapeutic strategies, which may help promote cancer immunotherapy.

Keywords: B-lymphocytes; humoral immunity; immunotherapy; prognosis; tertiary lymphoid structures; tumor microenvironment; tumor-infiltrating lymphocytes.

Figure 1

The migration pathways and diverse properties of TLS- and non-TLS-associated B cells in the TME. Naïve B cells are recruited and infiltrate into the TME via HEVs, mainly locating in the mantle zone of TLSs. After exposure to tumor antigens within the GCs, B cells interact with follicular helper T cells as well as follicular dendritic cells, and undergo a series of biological events, including clonal expansion, somatic hypermutation, class switching, and tumor-specific antibody production. Effector B cells or plasma cells elicit antitumor responses via direct tumor killing, antigen presentation, and antibody-mediated tumor cell lysis. In contrast, Bregs impair antitumor immunity through immunosuppressive cytokines, which inhibit the activity of T cells as well as NK cells, and induce Tregs, MDSCs, and angiogenesis.

Figure 2

Prognostic value of CD20⁺ TIBs according to cancer type. Bars represent the number of cohorts with positive (green), no effect (white), or negative (red) prognostic significance for the indicated cancer types. We searched PubMed for peer-reviewed articles reporting on the prognostic value in human solid tumors due to the obvious confounding issues. The following search terms and logic gates were used for the PubMed search: “B-cell” AND “cancer” AND “prognosis”.