Rapamycin Induces Phenotypic Alterations in Oral Cancer Cells That May Facilitate Antitumor T Cell Responses

• Published in: Biomedicines 2024-05, Vol.12 (5), p.1078
• Main 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
• Format: Article
• Language: English
• Subjects: Angiogenesis; Antitumor activity; Apoptosis; B cells; Cancer; Cancer therapies; Carbon dioxide; CD4 antigen; CD40 antigen; CD8 antigen; CD83 antigen; CD86 antigen; Cell adhesion molecules; Cell death; Cell migration; Cell proliferation; Cell surface; Cells; Chemotherapy; Dendritic cells; Flow cytometry; Health aspects; immune checkpoint inhibitor; Immune response (cell-mediated); Immunomodulation; Immunoregulation; immunotherapy; Intercellular adhesion molecule 1; Lymphocytes T; Major histocompatibility complex; Metabolism; Metastasis; Monoclonal antibodies; Mouth cancer; mTOR; Oral cancer; oral squamous cell carcinoma; P-selectin; PD-L1 protein; Prevention; Radiation therapy; Radiotherapy; Rapamycin; Scientific equipment and supplies industry; Squamous cell carcinoma; Suppressor cells; T cells; TOR protein; Tumors
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12051078

In this study, we investigated the antitumor immunomodulatory effects of rapamycin in oral cancer. 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. 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. Our results suggest that the therapeutic effect of mTOR inhibition in oral cancer can cause direct antitumor and immunomodulatory effects.