Journal article
SETDB1: a perspective into immune cell function and cancer immunotherapy
Immunology, Vol.169(1), pp.3-12
05/2023
DOI: 10.1111/imm.13619
PMCID: PMC10121739
PMID: 36524435
Appears in UI Libraries Support Open Access
Abstract
Oncogene SETDB1/ ESET, an H3K9 methyltransferase, was originally discovered over two decades ago, however its function in the immune response was not first reported until 2011. SETDB1 immune functions include B cell maturation, T cell activity regulation, and immune escape in cancer cells. In B lymphocytes, SETDB1 mediates the transition from pro-B to pre-B cells and represses endogenous retroviruses (ERV) to encourage B cell lineage differentiation and maturation. SETDB1 alters T cell function by methylating IL-2 and IL-17 promoters and mediating T cell lineage commitment and development. Additionally, SETDB1 plays a critical role in ERV silencing within a variety of immune cells, which can indirectly weaken the immune response. Although SETDB1 is critical for normal immune cell function, overexpression in cancer cells negatively impacts immune cell fights against cancer through decreased tumor immunogenicity. Within cancer cells, SETDB1 overexpression represses production and infiltration of antitumor immune cells, mediates immune escape through TE and ERV silencing, represses the type I interferon pathway, and interferes in immune checkpoint blockade (ICB) outcomes by regulation of PD-L1 expression and IFN signaling. In this review, we further discuss the immunological mechanisms of SETDB1 in normal and cancerous cells and its implications in cancer immunotherapy.
Details
- Title: Subtitle
- SETDB1: a perspective into immune cell function and cancer immunotherapy
- Creators
- Eleanor Johnson - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, USAKiarash Salari - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, USAShujie Yang - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Immunology, Vol.169(1), pp.3-12
- DOI
- 10.1111/imm.13619
- PMID
- 36524435
- PMCID
- PMC10121739
- NLM abbreviation
- Immunology
- ISSN
- 0019-2805
- eISSN
- 1365-2567
- Publisher
- Wiley
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R37CA238274; DOI: 10.13039/100015515, name: Roy J. and Lucille A. Carver College of Medicine, University of Iowa
- Language
- English
- Electronic publication date
- 12/16/2022
- Date published
- 05/2023
- Academic Unit
- Pathology
- Record Identifier
- 9984333160302771
Metrics
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