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

Johannes Griss, Wolfgang Bauer, Christine Wagner, Margarita Maurer-Granofszky, Martin Simon, Minyi Chen, Peter Steinberger, Katharina Grabmeier-Pfistershammer, Florian Roka, Thomas Penz, Christoph Bock, Gao Zhang, Meenhard Herlyn, Katharina Glatz, Heinz Läubli, Kirsten D Mertz, Peter Petzelbauer, Thomas Wiesner, Markus Hartl, Winfried F Pickl, Rajasekharan Somasundaram, Stephan N Wagner

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Jan 14, 2019
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Received Date: 23rd December 18

Tumor associated inflammation predicts response to immune checkpoint blockade in human melanoma. Established mechanisms that underlie therapy response and resistance center on anti-tumor T cell responses. 
Here we show that tumor-associated B cells are vital to tumor associated inflammation. Autologous B cells were directly induced by melanoma conditioned medium, expressed pro- and anti-inflammatory factors, and differentiated towards a plasmablast-like phenotype in vitro. We could identify this phenotype as a distinct cluster of B cells in an independent public single-cell RNA-seq dataset from melanoma tumors. There, plasmablast-like tumor-associated B cells showed expression of CD8+T cell-recruiting chemokines such as CCL3, CCL4, CCL5 and CCL28. Depletion of tumor associated B cells in metastatic melanoma patients by anti-CD20 immunotherapy decreased overall inflammation and CD8+T cell numbers in the human melanoma TME. Conversely, the frequency of plasmablast-like B cells in pretherapy melanoma samples predicted response and survival to immune checkpoint blockade in two independent cohorts. Tumor-associated B cells therefore orchestrate and sustain tumor inflammation, recruit CD8+ T effector cells and may represent a predictor for response and survival to immune checkpoint blockade in human melanoma.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.


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