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B Cells Sustain Inflammation and Predict Response to Immune Checkpoint Blockade in Human Melanoma

B Cells Sustain Inflammation and Predict Response to Immune Checkpoint Blockade in Human Melanoma

Johannes Griss, Wolfgang Bauer, Christine Wagner, Martin Simon, Minyi Chen, Katharina Grabmeier-Pfistershammer, Margarita Maurer-Granofszky, Florian Roka, Thomas Penz, Christoph Bock, Gao Zhang, Meenhard Herlyn, etc.

Nat Commun. 2019 Sep 13;10(1):4186.

PMID: 31519915

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248676	MIP-1beta human			Price

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