https://scholars.lib.ntu.edu.tw/handle/123456789/638303
標題: | Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy | 作者: | Lee, Yi-Mei Hsu, Chia-Lang Chen, Yu-Hsin DA-LIANG OU CHIUN HSU Tan, Ching-Ting |
公開日期: | 1-十一月-2023 | 卷: | 11 | 期: | 11 | 來源出版物: | Cancer immunology research | 摘要: | The immune checkpoint inhibitor (ICI), anti-programmed death-1 (anti-PD-1), has shown moderate efficacy in some patients with head and neck squamous cell carcinoma (HNSCC). Because of this, it is imperative to establish a mouse tumor model to explore mechanisms of antitumor immunity and to develop novel therapeutic options. Here, we examined the 4-nitroquinoline-1-oxide (4NQO)-induced oral squamous cell carcinoma (OSCC) model for genetic aberrations, transcriptomic profiles, and immune cell composition at different pathologic stages. Genomic exome analysis in OSCC-bearing mice showed conservation of critical mutations found in human HNSCC. Transcriptomic data revealed that a key signature comprised of immune-related genes was increased beginning at the moderate dysplasia stages. We first identified that macrophage composition in primary tumors differed across pathologic stages, leading to an oncogenic evolution through a change in the M1/M2 macrophage ratio during tumorigenesis. We treated the 4NQO-induced OSCC-bearing mice with anti-PD-1 and agonistic anti-CD40, which modulated multiple immune responses. The growth of tumor cells was significantly decreased by agonistic anti-CD40 by promoting an increase in the M1/M2 ratio. By examining cross-species genomic conservation in human and mouse tumors, our study demonstrates the molecular mechanisms underlying the development of OSCC and the regulation of contributing immune-related factors, and aims to facilitate the development of suitable ICI-based treatments for patients with HNSCC. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/638303 | ISSN: | 23266066 | DOI: | 10.1158/2326-6066.CIR-23-0133 |
顯示於: | 腫瘤醫學研究所 |
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