Resveratrol induces major histocompatibility complex class I antigen presentation in a STING-dependent and independent manner in melanoma.

Autor: Morehead LC; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Koss B; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Fil D; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Heflin B; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Garg S; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Wallis KF; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Tackett AJ; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: ajtackett@uams.edu., Miousse IR; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: iracinemiousse@uams.edu.
Jazyk: angličtina
Zdroj: Molecular immunology [Mol Immunol] 2023 Nov; Vol. 163, pp. 188-195. Date of Electronic Publication: 2023 Oct 12.
DOI: 10.1016/j.molimm.2023.10.003
Abstrakt: Immune checkpoint inhibitor therapy has drastically improved outcomes in treating cancer, particularly in melanoma. However, half of melanoma patients are resistant to treatment. One mechanism used by tumor cells to evade immune attack is to down-regulate major histocompatibility complex (MHC) class I molecules, which are required for cytotoxic CD8 T-cells to eliminate cancer cells. To increase immunotherapeutic efficacy, it is critical to identify how to restore MHC-I expression on cancer cells so that tumor antigens are presented. We found that resveratrol elevated MHC-I expression, so that tumor antigens are presented to cytotoxic CD8 T-cell killing. Through proteomic interrogation, we identified the STING pathway as a potential mechanism of action. Further studies indicated that resveratrol-mediated regulation of STING induced MHC-I expression potentially through both interferon-independent and dependent pathways. Our results have indicated the potential of STING to induce MHC-I expression independent of interferon signaling, broadening the potential of STING modulation as a tool to improve immune checkpoint blockade.
Competing Interests: Declaration of Competing Interest L.C.M. has holdings in Bristol-Myers-Squibb.
(Published by Elsevier Ltd.)
Databáze: MEDLINE
Externí odkaz: