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

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 May 25

PMID 38791040

Authors

Amirmoezz Yonesi

Kei Tomihara

Danki Takatsuka

Hidetake Tachinami

Manabu Yamazaki

Amir Reza Younesi Jadidi

Mayu Takaichi

Shuichi Imaue

Kumiko Fujiwara

Shin-Ichi Yamada

Jun-Ichi Tanuma

Makoto Noguchi

Affiliations

Soon will be listed here.

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.

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