B cell activating factor (BAFF) attenuates immunosuppressive monocytes in the melanoma tumor micro-environment

Emerging evidence indicates BAFF to be an important cytokine influencing anti-tumoral immunity. We generated a BAFF-overexpressing B16.F10 (BAFF) melanoma cell model and found that a significant survival advantage was conferred to C57BL/6 mice inoculated with BAFF cells. BAFF tumors had decreased myeloid infiltrates with lower PD-L1 expression. Monocyte depletion and anti-PD-L1 antibody treatment confirmed the functional significance on the phenotype. RNA-Seq analysis confirmed that monocytes isolated from BAFF tumors where characterized by a decreased exhaustive phenotype and enriched for in genes activating adaptive immune responses and NF-𝜅𝛽 signaling. We wondered about the clinical relevance of BAFF plasma levels in melanoma patients. Evaluation of late stage metastatic melanoma patients treated with inhibitors of the PD-1/PD-L1 axis demonstrated a stratification of patients with high and low BAFF plasma levels, the former of which experienced lower responses to anti-PD-1 immunotherapies. In summary, we have shown that BAFF, through effects on tumor infiltrating monocytes not only impacts primary tumor growth but as biomarker can contribute to predicting response to anti-PD1 immunotherapy in later stages of advanced disease. C57BL/6 mice were inoculated subcutaneously with BAFF or control cells. 13 days post-inoculation, monocytes were sorted from BAFF and control tumors. Isolated monocytes were analyzed using RNA-Seq analysis