B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma

Griss, Bauer, Wagner, Simon, Chen, Grabmeier-Pfistershammer, Maurer-Granofszky, Roka, Penz, Bock, Zhang, Herlyn, Glatz, Läubli, Mertz, Petzelbauer, Wiesner, Hartl, Pickl, Somasundaram, Steinberger, Wagner (2019) B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma Nat Commun (IF: 16.6) 10(1) 4186

Abstract

Tumor associated inflammation predicts response to immune checkpoint blockade in human melanoma. Current theories on regulation of inflammation center on anti-tumor T cell responses. Here we show that tumor associated B cells are vital to melanoma associated inflammation. Human B cells express pro- and anti-inflammatory factors and differentiate into plasmablast-like cells when exposed to autologous melanoma secretomes in vitro. This plasmablast-like phenotype can be reconciled in human melanomas where plasmablast-like cells also express T cell-recruiting chemokines CCL3, CCL4, CCL5. Depletion of B cells in melanoma patients by anti-CD20 immunotherapy decreases tumor associated inflammation and CD8+ T cell numbers. Plasmablast-like cells also increase PD-1+ T cell activation through anti-PD-1 blockade in vitro and their frequency in pretherapy melanomas predicts response and survival to immune checkpoint blockade. Tumor associated B cells therefore orchestrate and sustain melanoma inflammation and may represent a predictor for survival and response to immune checkpoint blockade therapy.

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744450
http://www.ncbi.nlm.nih.gov/pubmed/31519915
http://dx.doi.org/10.1038/s41467-019-12160-2

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