Inflammatory B cells correlate with failure to checkpoint blockade in melanoma patients
Kaat de Jonge, Laure Tillé, João Lourenço, Hélène Maby–El Hajjami, Sina Nassiri, Julien Racle, David Gfeller, Mauro Delorenzi, Grégory Verdeil, Petra Baumgaertner, Daniel E. Speiser
Abstract
The understanding of the role of B cells in patients with solid tumors remains insufficient. We found that circulating B cells produced TNFα and/or IL-6, associated with unresponsiveness and poor overall survival of melanoma patients treated with anti-CTLA4 antibody. Transcriptome analysis of B cells from melanoma metastases showed enriched expression of inflammatory response genes. Publicly available single B cell data from the tumor microenvironment revealed a negative correlation between TNFα expression and response to immune checkpoint blockade. These findings suggest that B cells contribute to tumor growth via the production of inflammatory cytokines. Possibly, these B cells are different from tertiary lymphoid structure-associated B cells, which have been described to correlate with favorable clinical outcome of cancer patients. Further studies are required to identify and characterize B cell subsets and their functions promoting or counteracting tumor growth, with the aim to identify biomarkers and novel treatment targets.