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

doi:10.1016/j.celrep.2024.113872

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

Cell Rep. 2024 Mar 26;43(3):113872. doi: 10.1016/j.celrep.2024.113872. Epub 2024 Feb 29.

Authors

Daniel G Chen¹, Jingyi Xie², Jongchan Choi³, Rachel H Ng⁴, Rongyu Zhang⁴, Sarah Li³, Rick Edmark³, Hong Zheng⁵, Ben Solomon⁶, Katie M Campbell⁷, Egmidio Medina⁸, Antoni Ribas⁹, Purvesh Khatri⁵, Lewis L Lanier¹⁰, Philip J Mease¹¹, Jason D Goldman¹², Yapeng Su¹³, James R Heath¹⁴

Affiliations

¹ 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.
² Institute of Systems Biology, Seattle, WA, USA; Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, USA.
³ Institute of Systems Biology, Seattle, WA, USA.
⁴ Institute of Systems Biology, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA.
⁵ 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.
⁶ Department of Pediatrics, Division of Allergy and Immunology, Stanford School of Medicine, Stanford, CA, USA.
⁷ 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.
⁸ Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA, USA.
⁹ 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.
¹⁰ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
¹¹ Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, USA; Providence St. Joseph Health, Renton, WA, USA.
¹² 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.
¹³ 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.
¹⁴ 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. Electronic address: [email protected].

Abstract

Infection, autoimmunity, and cancer are principal human health challenges of the 21^st 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 (T_RM) 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 T_RM cells. Our results suggest NKG2A⁺ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.

Keywords: CD8(+) T cells; CP: Immunology; NKG2A; autoimmune disease; cancer; infectious disease; multi-disease; plasma proteomics; single-cell multi-omics; systems immunology.

MeSH terms

Autoimmune Diseases* / pathology
Autoimmunity
CD8-Positive T-Lymphocytes
Communicable Diseases* / pathology
Humans
Immunologic Memory
Inflammation / pathology
Neoplasms* / pathology

Abstract

MeSH terms

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