Liu, Wei and Stachura, Pawel and Xu, Haifeng C. and Varaljai, Renata and Shinde, Prashant and Ganesh, Nikkitha Umesh and Mack, Matthias and Van Lierop, Anke and Huang, Anfei and Sundaram, Balamurugan and Lang, Karl S. and Picard, Daniel and Fischer, Ute and Remke, Marc and Homey, Bernhard and Roesch, Alexander and Haeussinger, Dieter and Lang, Philipp A. and Borkhardt, Arndt and Pandyra, Aleksandra A. (2022) BAFF Attenuates Immunosuppressive Monocytes in the Melanoma Tumor Microenvironment. CANCER RESEARCH, 82 (2). pp. 264-277. ISSN 0008-5472, 1538-7445
Full text not available from this repository. (Request a copy)Abstract
Emerging evidence indicates B-cell activating factor (BAFF, Tnfsf13b) to he 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-kappa B 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | B-LYMPHOCYTE STIMULATOR; T-CELL; DISEASE PROGRESSION; PD-L1 EXPRESSION; HODGKIN-LYMPHOMA; RECEPTOR; CANCER; EFFICACY; BLYS; ACTIVATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Feb 2024 07:44 |
| Last Modified: | 01 Feb 2024 07:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58493 |
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