Effects of B cell-activating factor on tumor immunity.

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
• Journal: JCI insight (JCI Insight) Vol. 5 Issue 10 (05 21 2020) ISSN: 2379-3708 [Electronic] United States
• PMID: 32434989 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• B-Cell Activating Factor
• IFNG protein, mouse
• Il12a protein, mouse
• Interleukin-12 Subunit p35
• Tnfsf13b protein, mouse
• Interferon-gamma

Topics

• Animals
• B-Cell Activating Factor (genetics, immunology)
• Immunity, Cellular
• Interferon-gamma (immunology)
• Interleukin-12 Subunit p35 (genetics, immunology)
• Melanoma, Experimental (genetics, immunology, pathology)
• Mice
• T-Lymphocytes, Regulatory (immunology)
• Th1 Cells (immunology)