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

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Sep 15

PMID 31519915

Citations 192

Authors

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

Katharina Glatz

Heinz Laubli

Kirsten D Mertz

Peter Petzelbauer

Thomas Wiesner

Markus Hartl

Winfried F Pickl

Rajasekharan Somasundaram

Peter Steinberger

Stephan N Wagner

Affiliations

Soon will be listed here.

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.

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