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Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy

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 n...

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Autores principales: Lee, Yi-Mei, Hsu, Chia-Lang, Chen, Yu-Hsin, Ou, Da-Liang, Hsu, Chiun, Tan, Ching-Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618654/
https://www.ncbi.nlm.nih.gov/pubmed/37669022
http://dx.doi.org/10.1158/2326-6066.CIR-23-0133
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author Lee, Yi-Mei
Hsu, Chia-Lang
Chen, Yu-Hsin
Ou, Da-Liang
Hsu, Chiun
Tan, Ching-Ting
author_facet Lee, Yi-Mei
Hsu, Chia-Lang
Chen, Yu-Hsin
Ou, Da-Liang
Hsu, Chiun
Tan, Ching-Ting
author_sort Lee, Yi-Mei
collection PubMed
description 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.
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spelling pubmed-106186542023-11-02 Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy Lee, Yi-Mei Hsu, Chia-Lang Chen, Yu-Hsin Ou, Da-Liang Hsu, Chiun Tan, Ching-Ting Cancer Immunol Res Research Articles 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. American Association for Cancer Research 2023-11-01 2023-09-05 /pmc/articles/PMC10618654/ /pubmed/37669022 http://dx.doi.org/10.1158/2326-6066.CIR-23-0133 Text en ©2023 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Research Articles
Lee, Yi-Mei
Hsu, Chia-Lang
Chen, Yu-Hsin
Ou, Da-Liang
Hsu, Chiun
Tan, Ching-Ting
Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy
title Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy
title_full Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy
title_fullStr Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy
title_full_unstemmed Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy
title_short Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy
title_sort genomic and transcriptomic landscape of an oral squamous cell carcinoma mouse model for immunotherapy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618654/
https://www.ncbi.nlm.nih.gov/pubmed/37669022
http://dx.doi.org/10.1158/2326-6066.CIR-23-0133
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