Tumor-infiltrating B cells in cancer immunity: heterogeneity, spatial organization, and context-dependent function.

Abstract

Tumor-infiltrating B cells are emerging as critical regulators of cancer immunity. Recent single-cell and spatial studies have shown that their functions extend beyond antibody production to include antigen presentation, tertiary lymphoid structure (TLS) organization, T cell modulation, cytokine-mediated regulation, and myeloid crosstalk. However, the clinical and immunological roles of B cells in cancer are highly context-dependent. In some tumors, B cell infiltration, particularly within mature TLSs, is associated with improved survival and enhanced responses to immune checkpoint blockade. In other settings, regulatory B cells or immunosuppressive plasma cells can promote tumor progression by suppressing cytotoxic lymphocytes, reinforcing regulatory immune networks, or cooperating with suppressive myeloid populations. These divergent observations indicate that B cells should not be interpreted as uniformly anti-tumor or pro-tumor. Instead, their functions are shaped by developmental state, spatial localization, inflammatory cues, antigenic specificity, and cellular interaction networks. In this review, we discuss tumor-infiltrating B cells through a context-dependent framework. We propose that B cells support anti-tumor immunity when integrated into organized lymphoid niches and engaged in productive T cell-B cell cooperation, whereas they promote immune escape when redirected toward regulatory programs or suppressive myeloid interactions. Understanding this functional plasticity may help reconcile differences across cancer types and guide the development of B cell-informed biomarkers and therapeutic strategies.