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

Nat Commun. 2019 Sep 13;10(1):4186. doi: 10.1038/s41467-019-12160-2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Monoclonal / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Chemokine CCL3 / metabolism
  • Chemokine CCL4 / metabolism
  • Chemokine CCL5 / metabolism
  • Humans
  • Immunotherapy
  • In Vitro Techniques
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Melanoma / immunology
  • Melanoma / metabolism*
  • Melanoma / therapy
  • Programmed Cell Death 1 Receptor / metabolism


  • Antibodies, Monoclonal
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Programmed Cell Death 1 Receptor