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PARP11 interfer(on)es with CAR T cell efficacy.
Nat Cancer
July 2022
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors.
Nat Cancer
July 2022
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Article Synopsis
- Evasion of tumor immunity and resistance to treatments in solid tumors is supported by an immunosuppressive tumor microenvironment (TME), characterized by factors like regulatory T cells and adenosine.
- The study identified that these TME factors downregulate the IFNAR1 receptor on CD8 cytotoxic T lymphocytes (CTLs) through the action of PARP11, which is increased in CTLs within tumors.
- Inhibition of PARP11 not only maintains IFNAR1 levels but also boosts CTL activity against tumors, enhancing the effectiveness of chimeric antigen receptor (CAR) T cell therapies.
ADP-ribosyltransferase PARP11 suppresses Zika virus in synergy with PARP12.
Cell Biosci
June 2021
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
Article Synopsis
- Zika virus poses significant global health threats, leading to severe congenital neurological issues like microcephaly, and the Type I interferon response helps control its replication by activating interferon-stimulated genes (ISGs).
- The study investigates the role of PARP11 in combating Zika virus by creating cell lines to analyze its anti-Zika function and its interaction with PARP12 in degrading viral proteins NS1 and NS3.
- Results show that PARP11 is induced by interferon signaling and viral infection, suppresses Zika replication independently of its enzyme activity, and works with PARP12 to enhance the degradation of viral proteins, revealing potential therapeutic targets against ZIKV.
PARP11 regulates total levels of type-I interferon receptor IFNAR1.
Nat Microbiol
November 2019
International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
ADP-ribosyltransferase PARP11 modulates the interferon antiviral response by mono-ADP-ribosylating the ubiquitin E3 ligase β-TrCP.
Nat Microbiol
November 2019
International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
Outbreaks of viral infections are a global health burden. Although type I interferon (IFN-I) exerts broad-spectrum antiviral effects, its antiviral efficacy in host cells is largely restricted by viruses. How the antiviral efficacy of IFN-I can be improved remains to be explored.
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