TY - JOUR
T1 - Effects of B cell-activating factor on tumor immunity
AU - Yarchoan, Mark
AU - Ho, Won Jin
AU - Mohan, Aditya
AU - Shah, Yajas
AU - Vithayathil, Teena
AU - Leatherman, James
AU - Dennison, Lauren
AU - Zaidi, Neeha
AU - Ganguly, Sudipto
AU - Woolman, Skylar
AU - Cruz, Kayla
AU - Armstrong, Todd D.
AU - Jaffee, Elizabeth M.
N1 - Funding Information:
We thank P. Schneider for support throughout the course of this work and other members of the Jaffee lab for critical discussion of the manuscript. We thank J. Donaldson for help constructing the 3T3-BAFF cell line. Some of the results presented here are derived from data generated by the TCGA Research Network: https://www.cancer.gov/tcga. MY is the recipient of the NCI Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancers Career Enhancement Award (2P50CA062924-24A1) and a grant from the Commonwealth Foundation. Additional support is recognized from the Johns Hopkins Bloomberg– Kimmel Institute for Cancer Immunotherapy and the NIH Center Core Grant (P30 CA006973).
Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI.INSIGHT.136417
DO - 10.1172/JCI.INSIGHT.136417
M3 - Article
C2 - 32434989
AN - SCOPUS:85085158471
SN - 2379-3708
VL - 5
JO - JCI Insight
JF - JCI Insight
IS - 10
M1 - e136417
ER -