B cells infiltrate tumors across a wide range of cancer types and exhibit considerable phenotypic and functional diversity. This review synthesizes current understanding of these tumor-infiltrating B cells, summarizing their classification, roles in tumor biology, signaling pathways, intercellular communications, and potential as therapeutic targets. The authors highlight the clinical relevance of B-cell features such as tertiary lymphoid structures and the antibody repertoire as indicators of immunotherapy response.
The review traces the historical trajectory of investigations into B cells within tumors, emphasizing how the field has evolved from characterizing simple infiltration to appreciating complex functional states. Over time, research moved from descriptive analyses to mechanistic studies that map B-cell subtypes, signaling networks, and interactions with other immune and stromal cells. This historical perspective frames current efforts to translate mechanistic insights into therapeutic strategies targeting tumor B cells.
A wide array of B-cell subtypes can be identified within tumors. These subpopulations confer adaptability and functional heterogeneity, enabling B cells to perform varied roles in the tumor microenvironment. The review analyzes classification frameworks used to distinguish B-cell states, noting that different subtypes are associated with distinct effector functions, secretory profiles, and capacities to participate in local lymphoid architecture.
Tumor-infiltrating B cells act as microenvironmental mediators through multiple mechanisms. Key activities described include formation of tertiary lymphoid structures, secretion of diverse soluble factors, and generation of a broad antibody repertoire. These functions can support antitumor immunity—by presenting antigen, facilitating T-cell responses, or producing tumor-reactive antibodies—or in other contexts contribute to tumor progression. The review emphasizes that B-cell impact on tumors is context-dependent and determined by subtype and local cues.
The review examines intracellular signaling pathways that shape B-cell differentiation and effector function within tumors, and it details how B cells communicate with other cell types in the microenvironment. Crosstalk with T cells, antigen-presenting cells, stromal elements, and the tumor itself modulates B-cell activity and, reciprocally, influences the behavior of neighboring cells. These signaling and interaction networks underpin the functional plasticity of tumor B cells.
B-cell phenotypes and functions are regulated at multiple levels by the tumor microenvironment. Local cytokines, chemokines, cell-cell contacts, and structural features such as lymphoid-like niches collectively control B-cell recruitment, survival, differentiation, and effector programming. The review outlines these multilevel regulatory inputs and how they integrate to produce diverse B-cell states observed in different malignancies.
Based on expression of surface molecules, including immune checkpoints and other accessible targets, tumor-infiltrating B cells present opportunities for therapeutic intervention. The review summarizes current understanding of exploitable targets on B cells and suggests that modulating B-cell function—either inhibiting protumoral activities or enhancing antitumor functions—may complement existing cancer therapies. Targeted strategies aim to reduce nonresponse, overcome drug resistance, and limit immune-related adverse events associated with current treatments.
Recent clinical trials and translational studies cited in the review indicate that intervening in tumor-infiltrating B cells can be effective across several common malignancies, including breast cancer, colorectal carcinoma, and non-small cell lung cancer. The authors report that B-cell features can serve as biomarkers of response and that modulating B-cell activity holds promise for improving therapeutic outcomes. Specific trial names, numeric outcomes, and detailed protocols were not provided in the source abstract.
The review concludes that tumor-infiltrating B cells are important but heterogeneous contributors to tumor biology with substantial therapeutic potential. Recognizing B cells as targets could inform strategies to enhance antitumor immunity and reduce treatment failure. The authors call for continued mechanistic research and clinical investigation to translate knowledge of B-cell subtypes, signaling, and regulatory networks into validated therapies and predictive biomarkers.