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- Title
B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma.
- Authors
Griss, Johannes; Bauer, Wolfgang; Wagner, Christine; Simon, Martin; Chen, Minyi; Grabmeier-Pfistershammer, Katharina; Maurer-Granofszky, Margarita; Roka, Florian; Penz, Thomas; Bock, Christoph; Zhang, Gao; Herlyn, Meenhard; Glatz, Katharina; Läubli, Heinz; Mertz, Kirsten D.; Petzelbauer, Peter; Wiesner, Thomas; Hartl, Markus; Pickl, Winfried F.; Somasundaram, Rajasekharan
- 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. The regulation of tumor inflammation is incompletely understood and the role of B cells is unclear. Here, the authors show that a specific subtype of B cells is induced in melanoma and required to recruit T lymphocytes and elicit inflammation.
- Subjects
B cells; INFLAMMATION; IMMUNE response; MELANOMA; T cells
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-12160-2