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- Title
Rapamycin Induces Phenotypic Alterations in Oral Cancer Cells That May Facilitate Antitumor T Cell Responses.
- Authors
Yonesi, Amirmoezz; Tomihara, Kei; Takatsuka, Danki; Tachinami, Hidetake; Yamazaki, Manabu; Jadidi, Amir Reza Younesi; Takaichi, Mayu; Imaue, Shuichi; Fujiwara, Kumiko; Yamada, Shin-Ichi; Tanuma, Jun-Ichi; Noguchi, Makoto
- Abstract
Objectives: In this study, we investigated the antitumor immunomodulatory effects of rapamycin in oral cancer. Study Design: We examined the proliferation, apoptosis, and migration of cancer cells and investigated the cell surface expression levels of immune accessory molecules and T cell immune responses in vitro. We investigated the effect of in vivo administration of rapamycin on immune cell distribution and T cell immune responses in oral tumor-bearing mice. Results: Rapamycin treatment significantly inhibited OSCC cell proliferation and migration, increased apoptotic cell death, and upregulated cell surface expression of several immune accessory and adhesion molecules, including CD40, CD83, PD-L1, PD-L2, MHC class I, P-selectin, and VCAM-1. These cancer cells augmented T cell proliferation. In vivo rapamycin administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T cells, CD8+ T cells, and dendritic cells (DCs); decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor cells and regulatory T cells; enhanced DC maturation and upregulated the surface expression of CD40, CD86, and ICAM-1. Conclusions: Our results suggest that the therapeutic effect of mTOR inhibition in oral cancer can cause direct antitumor and immunomodulatory effects.
- Subjects
RAPAMYCIN; T cells; REGULATORY T cells; PHENOTYPIC plasticity; CANCER cells; MYELOID-derived suppressor cells
- Publication
Biomedicines, 2024, Vol 12, Issue 5, p1078
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines12051078