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.

CD36, a fatty acid scavenger receptor expressed in tumors, is associated with a poor prognosis in several cancers. Our previous research demonstrated the involvement of CD36 in the proliferation and migration of oral squamous cell carcinoma (OSCC) cells. However, the clinical significance of CD36 expression in OSCC remains unclear. The purpose of this study was to evaluate the association between CD36 expression and the clinicopathological characteristics of OSCC patients. Immunohistochemical expression of CD36 was quantified using the H-score, and its association with clinicopathological characteristics was evaluated in 55 OSCC patients. The mean H-score for membrane-associated CD36 expression was 84.8. CD36 expression was significantly correlated with tumor stage, mode of invasion, differentiation, and recurrence of OSCC cells. Moreover, elevated CD36 expression was significantly correlated with a high rate of relapse. Univariate and multivariate analyses showed that CD36 expression was an independent risk factor for relapse. Moreover, The Cancer Genome Atlas (TCGA) dataset analysis revealed that CD36 expression may coexist with transcriptional activation of β-oxidation-related and epithelial–mesenchymal transition (EMT)-related pathways. These findings suggest that CD36 might serve as a predictive biomarker for OSCC malignancy and recurrence.