Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer
Year: 2024
Type: article
Abstract: The fatty acid receptor CD36 is expressed on various malignant cells and is suggested to contribute to tumor progression. CD36 is also expressed by several immune cells and involved in immune responses and may be a potential target in cancer immunotherapy. In this study, we investigated whether the selective inhibition of CD36 can inhibit tumor progression and facilitate an antitumor immune response in oral squamous carcinoma cells (OSCCs). We assessed the effects of sulfosuccinimidyl oleate sodium (SSO), a CD36 inhibitor, on the proliferation apoptosis and alteration in tumor cell surface expression levels of immune accessory molecules in vitro. We also assessed whether SSO-treated OSCCs could promote a T cell response via a Mixed Lymphocyte Reaction (MLR) assay. We also investigated the direct antitumor effects and immunomodulatory effects of SSO using a mouse oral cancer OSCC model. SSO treatment significantly inhibited OSCC proliferation, increased apoptotic cell death, and upregulated the cell surface expression of several immune accessory molecules, including CD83, MHC-Class II, and PD-L1. SSO-treated OSCCs augmented T cell proliferation following MLR. In vivo SSO administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T, CD8+ T, and dendritic cells; it also decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor and regulatory T cells. These results suggest that the selective inhibition of CD36 can induce direct and indirect antitumor effects by facilitating host antitumor immune responses in OSCCs.
DOI: 10.3390/ijms25179438
Institutions: University of Toyama, Hasanuddin University, Niigata University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,296
Awards: Elucidation of the molecular mechanisms in the microenvironment of oral cancer using single-cell RNA sequence analysis, Immune escape mechanisms induced by dead cell-derived ectopic nucleic acids in oral cancer, G4143925313, Development of a Novel Immunotherapy Targeting Tumor-Associated Immunosuppressive Cells in Oral Cancer, Development of Immunological therapeutic strategies targeting polymorphonuclear myeloid derived suppressor cells for Oral Cancer, G6665181872, Correlation between CD36-mediated fat metabolism and immunosuppression in oral squamous cell carcinoma
OpenAlex ID: W4402048503