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Volume 25
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Article

Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer

by
Mayu Takaichi
1,
Hidetake Tachinami
1,
Danki Takatsuka
1,
Amirmoezz Yonesi
1,
Kotaro Sakurai
1,
Muhammad Irfan Rasul
2,
Shuichi Imaue
1,
Shin-Ichi Yamada
1,
Muhammad Ruslin
2,
Manabu Yamazaki
3,
Jun-Ichi Tanuma
3,
Makoto Noguchi
1 and
Kei Tomihara
3,4,*
1
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama 930-0194, Japan
2
Department of Oral and Maxillofacial Surgery, Hasanuddin University, Makassar 90245, Indonesia
3
Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
4
Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(17), 9438; https://doi.org/10.3390/ijms25179438
Submission received: 5 July 2024 / Revised: 15 August 2024 / Accepted: 23 August 2024 / Published: 30 August 2024
(This article belongs to the Special Issue Functional Molecules in Tracing and Cancer Therapeutics)
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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.
Keywords: CD36; sulfosuccinimidyl oleate sodium; immunotherapy; oral squamous cell carcinoma CD36; sulfosuccinimidyl oleate sodium; immunotherapy; oral squamous cell carcinoma

Share and Cite

MDPI and ACS Style

Takaichi, M.; Tachinami, H.; Takatsuka, D.; Yonesi, A.; Sakurai, K.; Rasul, M.I.; Imaue, S.; Yamada, S.-I.; Ruslin, M.; Yamazaki, M.; et al. Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer. Int. J. Mol. Sci. 2024, 25, 9438. https://doi.org/10.3390/ijms25179438

AMA Style

Takaichi M, Tachinami H, Takatsuka D, Yonesi A, Sakurai K, Rasul MI, Imaue S, Yamada S-I, Ruslin M, Yamazaki M, et al. Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer. International Journal of Molecular Sciences. 2024; 25(17):9438. https://doi.org/10.3390/ijms25179438

Chicago/Turabian Style

Takaichi, Mayu, Hidetake Tachinami, Danki Takatsuka, Amirmoezz Yonesi, Kotaro Sakurai, Muhammad Irfan Rasul, Shuichi Imaue, Shin-Ichi Yamada, Muhammad Ruslin, Manabu Yamazaki, and et al. 2024. "Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer" International Journal of Molecular Sciences 25, no. 17: 9438. https://doi.org/10.3390/ijms25179438

APA Style

Takaichi, M., Tachinami, H., Takatsuka, D., Yonesi, A., Sakurai, K., Rasul, M. I., Imaue, S., Yamada, S.-I., Ruslin, M., Yamazaki, M., Tanuma, J.-I., Noguchi, M., & Tomihara, K. (2024). Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer. International Journal of Molecular Sciences, 25(17), 9438. https://doi.org/10.3390/ijms25179438

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