Group 2 innate lymphoid cells (ILC2) are essential to maintain tissue homeostasis.,In cancer, ILC2 can harbor both pro- and anti-tumorigenic functions but we know very little about their underlying mechanisms, nor whether they could be clinically relevant or targeted to improve patient outcomes.,Here, we found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis.,ILC2 are critical producers of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) which coordinate the recruitment and activation of eosinophils to enhance anti-tumor responses.,Tumor-infiltrating ILC2 expressed programmed cell death protein-1 (PD-1), which limited their intratumoral accumulation, proliferation and anti-tumor effector functions.,This inhibition could be overcome in vivo by combining IL-33-driven ILC2 activation with PD-1 blockade to significantly increase anti-tumor responses.,Together, our results identified ILC2 as a critical immune cell type involved in melanoma immunity and revealed a potential synergistic approach to harness ILC2 function for anti-tumor immunotherapies.
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.,The regulation of tumor inflammation is incompletely understood and the role of B cells is unclear.,Here, the authors show that a specific subtype of B cells is induced in melanoma and required to recruit T lymphocytes and elicit inflammation.