BAFF Attenuates Immunosuppressive Monocytes in the Melanoma Tumor Microenvironment.

Emerging evidence indicates B-cell activating factor (BAFF, Tnfsf13b) to be an important cytokine for antitumor immunity. In this study, we generated a BAFF-overexpressing B16.F10 melanoma cell model and found that BAFF-expressing tumors grow more slowly in vivo than control tumors. The tumor microenvironment (TME) of BAFF-overexpressing tumors had decreased myeloid infiltrates with lower PD-L1 expression. Monocyte depletion and anti-PD-L1 antibody treatment confirmed the functional importance of monocytes for the phenotype of BAFF-mediated tumor growth delay. RNA sequencing analysis confirmed that monocytes isolated from BAFF-overexpressing tumors were characterized by a less exhaustive phenotype and were enriched for in genes involved in activating adaptive immune responses and NF-κB signaling. Evaluation of patients with late-stage metastatic melanoma treated with inhibitors of the PD-1/PD-L1 axis demonstrated a stratification of patients with high and low BAFF plasma levels. Patients with high BAFF levels experienced lower responses to anti-PD-1 immunotherapies. In summary, these results show that BAFF, through its effect on tumor-infiltrating monocytes, not only impacts primary tumor growth but can serve as a biomarker to predict response to anti-PD-1 immunotherapy in advanced disease. SIGNIFICANCE: The BAFF cytokine regulates monocytes in the melanoma microenvironment to suppress tumor growth, highlighting the importance of BAFF in antitumor immunity. ©2021 The Authors; Published by the American Association for Cancer Research.

Citation

Wei Liu, Paweł Stachura, Haifeng C Xu, Renáta Váraljai, Prashant Shinde, Nikkitha Umesh Ganesh, Matthias Mack, Anke Van Lierop, Anfei Huang, Balamurugan Sundaram, Karl S Lang, Daniel Picard, Ute Fischer, Marc Remke, Bernhard Homey, Alexander Roesch, Dieter Häussinger, Philipp A Lang, Arndt Borkhardt, Aleksandra A Pandyra. BAFF Attenuates Immunosuppressive Monocytes in the Melanoma Tumor Microenvironment. Cancer research. 2022 Jan 15;82(2):264-277

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PMID: 34810198

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