To elucidate the nuanced role of B cells in antitumor immunity, Griss et al. uncovered 6 tumor-associated B cell subpopulations in human melanoma. Exposure of patient-derived B cells to melanoma-conditioned media induced a plasmablast-like B cell (TIPB) phenotype expressing both pro- and anti-inflammatory factors. The TIPB expression signature, validated in vivo with single-cell RNAseq, correlated with tumor inflammation, CD8+ T cell and macrophage numbers, overall survival, and response to anti-PD-1 in melanoma. Anti-CD20 antibody therapy in melanoma reduced not only B cells but also inflammation, T cells, macrophages, and Tregs.
Contributed by Alex Najibi
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.
Author Info: (1) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. johannes.griss@meduniwien.ac.at. EMBL-European Bioinformatics Institute, Wellcome Trust Genome C
Author Info: (1) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. johannes.griss@meduniwien.ac.at. EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, CB10 1SD Hinxton, Cambridge, UK. johannes.griss@meduniwien.ac.at. (2) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. (3) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. (4) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. (5) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. (6) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria. (7) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. Children's Cancer Research Institute, 1090, Vienna, Austria. (8) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. (9) CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria. (10) CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria. Department of Laboratory Medicine, Medical University of Vienna, 1090, Vienna, Austria. (11) Molecular & Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, PA, 19104-4265, USA. Department of Neurosurgery & The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, 27710, USA. (12) Molecular & Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, PA, 19104-4265, USA. (13) Institute of Pathology, University Hospital Basel, 4031, Basel, Switzerland. (14) Division of Medical Oncology, University Hospital Basel, 4031, Basel, Switzerland. (15) Institute of Pathology, Cantonal Hospital Baselland, 4410, Liestal, Switzerland. (16) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. (17) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. (18) Mass Spectrometry Facility, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna BioCenter (VBC), 1030, Vienna, Austria. (19) Division of Cellular Immunology and Immunohematology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria. (20) Molecular & Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, PA, 19104-4265, USA. (21) Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria. (22) Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria. stephan.wagner@meduniwien.ac.at.
