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Effects of B cell–activating factor on tumor immunity
Mark Yarchoan, … , Todd D. Armstrong, Elizabeth M. Jaffee
Mark Yarchoan, … , Todd D. Armstrong, Elizabeth M. Jaffee
Published May 21, 2020
Citation Information: JCI Insight. 2020;5(10):e136417. https://doi.org/10.1172/jci.insight.136417.
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Research Article Immunology Oncology

Effects of B cell–activating factor on tumor immunity

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Abstract

Immunotherapies that modulate T cell function have been firmly established as a pillar of cancer therapy, whereas the potential for B cells in the antitumor immune response is less established. B cell–activating factor (BAFF) is a B cell–activating cytokine belonging to the TNF ligand family that has been associated with autoimmunity, but little is known about its effects on cancer immunity. We find that BAFF upregulates multiple B cell costimulatory molecules; augments IL-12a expression, consistent with Be-1 lineage commitment; and enhances B cell antigen-presentation to CD4+ Th cells in vitro. In a syngeneic mouse model of melanoma, BAFF upregulates B cell CD40 and PD-L1 expression; it also modulates T cell function through increased T cell activation and TH1 polarization, enhanced expression of the proinflammatory leukocyte trafficking chemokine CCR6, and promotion of a memory phenotype, leading to enhanced antitumor immunity. Similarly, adjuvant BAFF promotes a memory phenotype of T cells in vaccine-draining lymph nodes and augments the antitumor efficacy of whole cell vaccines. BAFF also has distinct immunoregulatory functions, promoting the expansion of CD4+Foxp3+ Tregs in the spleen and tumor microenvironment (TME). Human melanoma data from The Cancer Genome Atlas (TCGA) demonstrate that BAFF expression is positively associated with overall survival and a TH1/IFN-γ gene signature. These data support a potential role for BAFF signaling as a cancer immunotherapy.

Authors

Mark Yarchoan, Won Jin Ho, Aditya Mohan, Yajas Shah, Teena Vithayathil, James Leatherman, Lauren Dennison, Neeha Zaidi, Sudipto Ganguly, Skylar Woolman, Kayla Cruz, Todd D. Armstrong, Elizabeth M. Jaffee

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Figure 2

BAFF-activated B cells have enhanced antigen-presentation (APC) abilities for CD4+ Th cells.

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BAFF-activated B cells have enhanced antigen-presentation (APC) abilitie...
(A) CD4+ T cells from OT-II mice stimulated with B cells presenting SLKISQAVHAAHAEINEAGR peptides in the presence of BAFF expressed higher levels of granzyme B, IFN-γ, and PD-1. (B and C) Representative histograms and summative graph demonstrating the increased ability of BAFF-activated B cells to present antigens and stimulate OT-II CD4+ T cell proliferation. The Rpo132 peptide is used as the negative control (n = 5 per group, **P < 0.01, ****P < 0.0001, 2-tailed unpaired t test).

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