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Supplementary materials and methods from BAFF Attenuates Immunosuppressive Monocytes in the Melanoma Tumor Microenvironment

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journal contribution
posted on 2023-04-06, 17:00 authored by 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

Supplementary materials and methods

Funding

Medizinische Fakultät, Heinrich-Heine-Universität Düsseldorf (HHU)

Deutsche Forschungsgemeinschaft (DFG)

Jürgen Manchot Stiftung (Jürgen Manchot Foundation)

Heinrich-Heine-Universität Düsseldorf (HHU)

José Carreras Leukämie-Stiftung (José Carreras Leukämie-Stiftung e.V.)

Katharina-Hardt-Foundation

Loewenstern

History

ARTICLE ABSTRACT

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. The BAFF cytokine regulates monocytes in the melanoma microenvironment to suppress tumor growth, highlighting the importance of BAFF in antitumor immunity.

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