Details

Autor(en) / Beteiligte

• Liu, Wei
• Stachura, Paweł
• Xu, Haifeng C
• Váraljai, Renáta
• Shinde, Prashant
• Ganesh, Nikkitha Umesh
• Mack, Matthias
• Van Lierop, Anke
• Huang, Anfei
• Sundaram, Balamurugan
• Lang, Karl S
• Picard, Daniel
• Fischer, Ute
• Remke, Marc
• Homey, Bernhard
• Roesch, Alexander
• Häussinger, Dieter
• Lang, Philipp A
• Borkhardt, Arndt
• Pandyra, Aleksandra A

Titel

BAFF Attenuates Immunosuppressive Monocytes in the Melanoma Tumor Microenvironment

Ist Teil von

• Cancer research (Chicago, Ill.), 2022-01, Vol.82 (2), p.264-277

Ort / Verlag

United States: American Association for Cancer Research

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Emerging evidence indicates B-cell activating factor (BAFF, ) 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 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.