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http://purl.uniprot.org/citations/38016719http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Backgrounds

G-protein-coupled receptor 84 (GPR84) marks a subset of myeloid-derived suppressor cells (MDSCs) with stronger immunosuppression in the tumor microenvironment. Yet, how GPR84 endowed the stronger inhibition of MDSCs to CD8+ T cells function is not well established. In this study, we aimed to identify the underlying mechanism behind the immunosuppression of CD8+ T cells by GPR84+ MDSCs.

Methods

The role and underlying mechanism that MDSCs or exosomes (Exo) regulates the function of CD8+ T cells were investigated using immunofluorescence, fluorescence activating cell sorter (FACS), quantitative real-time PCR, western blot, ELISA, Confocal, RNA-sequencing (RNA-seq), etc. In vivo efficacy and mechanistic studies were conducted with wild type, GPR84 and p53 knockout C57/BL6 mice.

Results

Here, we showed that the transfer of GPR84 from MDSCs to CD8+ T cells via the Exo attenuated the antitumor response. This inhibitory effect was also observed in GPR84-overexpressed CD8+ T cells, whereas depleting GPR84 elevated CD8+ T cells proliferation and function in vitro and in vivo. RNA-seq analysis of CD8+ T cells demonstrated the activation of the p53 signaling pathway in CD8+ T cells treated with GPR84+ MDSCs culture medium. While knockout p53 did not induce senescence in CD8+ T cells treated with GPR84+ MDSCs. The per cent of GPR84+ CD8+ T cells work as a negative indicator for patients' prognosis and response to chemotherapy.

Conclusions

These data demonstrated that the transfer of GPR84 from MDSCs to CD8+ T cells induces T-cell senescence via the p53 signaling pathway, which could explain the strong immunosuppression of GPR84 endowed to MDSCs."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.org/dc/terms/identifier"doi:10.1136/jitc-2023-007802"xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Fu Z."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Li F."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Li J."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Li M."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Li J.'"xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Liu J.'"xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Guo C."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Zhang Y."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Zhang Z."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Zhao M."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Zhao X."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/author"Qin G."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/name"J Immunother Cancer"xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/pages"e007802"xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/title"MDSCs-derived GPR84 induces CD8+ T-cell senescence via p53 activation to suppress the antitumor response."xsd:string
http://purl.uniprot.org/citations/38016719http://purl.uniprot.org/core/volume"11"xsd:string
http://purl.uniprot.org/citations/38016719http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/38016719
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