Format

Send to

Choose Destination
Cell. 2017 Jan 26;168(3):487-502.e15. doi: 10.1016/j.cell.2016.12.022. Epub 2017 Jan 19.

Systemic Immunity Is Required for Effective Cancer Immunotherapy.

Author information

1
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.
2
Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Pathology, The Sackler School of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel.
3
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
4
Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
5
Baxter Lab in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
6
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.
7
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.
8
Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94305, USA. Electronic address: edengleman@stanford.edu.

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.

KEYWORDS:

cancer immunotherapy; immune responses; immunotherapy; mass cytometry; secondary lymphoid organs; single-cell analysis; systems immunology; tumor immunology; tumor microenvironment

PMID:
28111070
PMCID:
PMC5312823
DOI:
10.1016/j.cell.2016.12.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center