B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma.
Journal Article (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
- PMC6744450
Electronic International Standard Serial Number (EISSN)
- 2041-1723
Digital Object Identifier (DOI)
- 10.1038/s41467-019-12160-2
Language
- eng
Conference Location
- England