SOCS1 is a critical checkpoint in immune homeostasis, inflammation and tumor immunity

Grace M Bidgood; Narelle Keating; Karen Doggett; Sandra E Nicholson

doi:10.3389/fimmu.2024.1419951

SOCS1 is a critical checkpoint in immune homeostasis, inflammation and tumor immunity

Front Immunol. 2024 Jun 14:15:1419951. doi: 10.3389/fimmu.2024.1419951. eCollection 2024.

Authors

Grace M Bidgood^{1

2}, Narelle Keating^{1

2}, Karen Doggett^{1

2}, Sandra E Nicholson^{1

2}

Affiliations

¹ Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
² Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia.

Abstract

The Suppressor of Cytokine Signaling (SOCS) family proteins are important negative regulators of cytokine signaling. SOCS1 is the prototypical member of the SOCS family and functions in a classic negative-feedback loop to inhibit signaling in response to interferon, interleukin-12 and interleukin-2 family cytokines. These cytokines have a critical role in orchestrating our immune defence against viral pathogens and cancer. The ability of SOCS1 to limit cytokine signaling positions it as an important immune checkpoint, as evidenced by the detection of detrimental SOCS1 variants in patients with cytokine-driven inflammatory and autoimmune disease. SOCS1 has also emerged as a key checkpoint that restricts anti-tumor immunity, playing both a tumor intrinsic role and impacting the ability of various immune cells to mount an effective anti-tumor response. In this review, we describe the mechanism of SOCS1 action, focusing on the role of SOCS1 in autoimmunity and cancer, and discuss the potential for new SOCS1-directed cancer therapies that could be used to enhance adoptive immunotherapy and immune checkpoint blockade.

Keywords: JAK-STAT; SOCS1; autoimmunity; cancer; cytokine; immunotherapy.

Publication types

Review

MeSH terms

Animals
Autoimmunity
Cytokines / immunology
Cytokines / metabolism
Homeostasis* / immunology
Humans
Inflammation* / immunology
Neoplasms* / immunology
Neoplasms* / therapy
Signal Transduction
Suppressor of Cytokine Signaling 1 Protein* / genetics
Suppressor of Cytokine Signaling 1 Protein* / metabolism

Substances

Suppressor of Cytokine Signaling 1 Protein
SOCS1 protein, human
Cytokines

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. GMB was supported by an Australian government Research Training Program Scholarship. NK was supported in part by an Australian government Research Training Program Scholarship and a Fulbright Scholarship. This review was written with support in part from NHMRC Ideas Grant 2011761, Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme (IRIISS).