Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer

Daniel G. Chen; Jingyi Xie; Jongchan Choi; Rachel H. Ng; Rongyu Zhang; Sarah Li; Rick Edmark; Hong Zheng; Ben Solomon; Katie M. Campbell; Egmidio Medina; Antoni Ribas; Purvesh Khatri; Lewis L. Lanier; Philip J. Mease; Jason D. Goldman; Yapeng Su; James R. Heath

Cell Reports (Mar 2024)

Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer

Daniel G. Chen,
Jingyi Xie,
Jongchan Choi,
Rachel H. Ng,
Rongyu Zhang,
Sarah Li,
Rick Edmark,
Hong Zheng,
Ben Solomon,
Katie M. Campbell,
Egmidio Medina,
Antoni Ribas,
Purvesh Khatri,
Lewis L. Lanier,
Philip J. Mease,
Jason D. Goldman,
Yapeng Su,
James R. Heath

Affiliations

Daniel G. Chen: Institute of Systems Biology, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Jingyi Xie: Institute of Systems Biology, Seattle, WA, USA; Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, USA
Jongchan Choi: Institute of Systems Biology, Seattle, WA, USA
Rachel H. Ng: Institute of Systems Biology, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA
Rongyu Zhang: Institute of Systems Biology, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA
Sarah Li: Institute of Systems Biology, Seattle, WA, USA
Rick Edmark: Institute of Systems Biology, Seattle, WA, USA
Hong Zheng: Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA
Ben Solomon: Department of Pediatrics, Division of Allergy and Immunology, Stanford School of Medicine, Stanford, CA, USA
Katie M. Campbell: Department of Medicine, Division of Hematology–Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA
Egmidio Medina: Department of Medicine, Division of Hematology–Oncology, University of California, Los Angeles, Los Angeles, CA, USA
Antoni Ribas: Department of Medicine, Division of Hematology–Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA
Purvesh Khatri: Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA
Lewis L. Lanier: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA
Philip J. Mease: Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, USA; Providence St. Joseph Health, Renton, WA, USA
Jason D. Goldman: Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, USA; Providence St. Joseph Health, Renton, WA, USA; Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA
Yapeng Su: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
James R. Heath: Institute of Systems Biology, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 3
p. 113872

Abstract

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Summary: Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation and increased humoral immunity and that they resemble TRM cells. Our results suggest NKG2A+ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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