title: Systemic Immunity Is Required for Effective Cancer Immunotherapy.
abstract: Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection.
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA; Baxter Lab in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: matthew.spitzer@ucsf.edu.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Spitzer
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Pathology, The Sackler School of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Carmi
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Reticker-Flynn
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Serena S
authors.initials: SS
authors.lastname: Kwek
authors.affiliation: Baxter Lab in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Madhireddy
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Martins
authors.affiliation: Baxter Lab in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Pier Federico
authors.initials: PF
authors.lastname: Gherardini
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Tyler R
authors.initials: TR
authors.lastname: Prestwood
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chabon
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Bendall
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fong
authors.affiliation: Baxter Lab in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94305, USA. Electronic address: gnolan@stanford.edu.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Nolan
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94305, USA. Electronic address: edengleman@stanford.edu.
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Engleman
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D001853:Bone Marrow / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D064726:Triple Negative Breast Neoplasms / Q000276:immunology / Q000628:therapy; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen
keywords: cancer immunotherapy; immune responses; immunotherapy; mass cytometry; secondary lymphoid organs; single-cell analysis; systems immunology; tumor immunology; tumor microenvironment