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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Griss, J; Bauer, W; Wagner, C; Simon, M; Chen, M; Grabmeier-Pfistershammer, K; Maurer-Granofszky, M; Roka, F; Penz, T; Bock, C; Zhang, G; Herlyn, M; Glatz, K; Läubli, H; Mertz, KD; Petzelbauer, P; Wiesner, T; Hartl, M; Pickl, WF; Somasundaram, R; Steinberger, P; Wagner, SN

Published Date

  • September 13, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 4186 -

PubMed ID

  • 31519915

Pubmed Central ID

  • 31519915

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-12160-2

Language

  • eng

Conference Location

  • England