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Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer
Mayu Takaichi1, Hidetake Tachinami1, Danki Takatsuka1
1Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama 930-0194, Japan.
Selective inhibition of the fatty acid receptor CD36 using sulfosuccinimidyl oleate sodium (SSO) suppressed oral squamous cell carcinoma (OSCC) progression. SSO also enhanced antitumor immunity by promoting T cell responses and reducing immune-suppressive cells.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- The fatty acid receptor CD36 is implicated in tumor progression and immune responses.
- CD36's role in oral squamous cell carcinoma (OSCC) and its potential as an immunotherapy target require further investigation.
Purpose of the Study:
- To investigate the effects of selective CD36 inhibition on OSCC progression and antitumor immunity.
- To assess the potential of sulfosuccinimidyl oleate sodium (SSO) as a CD36 inhibitor in OSCC.
Main Methods:
- In vitro assessment of SSO's effects on OSCC proliferation, apoptosis, and immune accessory molecule expression.
- Mixed Lymphocyte Reaction (MLR) assay to evaluate SSO-treated OSCCs' ability to promote T cell response.
- In vivo study using a mouse OSCC model to assess SSO's antitumor and immunomodulatory effects.
Main Results:
- SSO significantly inhibited OSCC proliferation and induced apoptosis in vitro.
- SSO upregulated immune accessory molecules (CD83, MHC-Class II, PD-L1) on OSCCs and augmented T cell proliferation in MLR.
- In vivo, SSO attenuated tumor growth, increased effector immune cells (CD4+, CD8+ T cells, dendritic cells), and decreased suppressive cells (MDSCs, Tregs).
Conclusions:
- Selective CD36 inhibition by SSO demonstrates direct antitumor effects in OSCC.
- SSO facilitates host antitumor immune responses, suggesting its potential in cancer immunotherapy for OSCC.
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