Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review

The tumor microenvironment (TME) plays a crucial role in the development, progression, and metastasis of oral squamous cell carcinoma (OSCC). The TME comprises various cellular and acellular components, including immune cells, stromal cells, cytokines, extracellular matrix, and the oral microbiome,...

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Main Authors: Laertty Garcia de Sousa Cabral, Isabela Mancini Martins, Ellen Paim de Abreu Paulo, Karina Torres Pomini, Jean-Luc Poyet, Durvanei Augusto Maria
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/5/621
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author Laertty Garcia de Sousa Cabral
Isabela Mancini Martins
Ellen Paim de Abreu Paulo
Karina Torres Pomini
Jean-Luc Poyet
Durvanei Augusto Maria
author_facet Laertty Garcia de Sousa Cabral
Isabela Mancini Martins
Ellen Paim de Abreu Paulo
Karina Torres Pomini
Jean-Luc Poyet
Durvanei Augusto Maria
author_sort Laertty Garcia de Sousa Cabral
collection DOAJ
description The tumor microenvironment (TME) plays a crucial role in the development, progression, and metastasis of oral squamous cell carcinoma (OSCC). The TME comprises various cellular and acellular components, including immune cells, stromal cells, cytokines, extracellular matrix, and the oral microbiome, all of which dynamically interact with tumor cells to influence their behavior. Immunosuppression is a key feature of the OSCC TME, with regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) contributing to an environment that allows tumor cells to evade immune surveillance and supports angiogenesis. The oral microbiome also plays a pivotal role in OSCC pathogenesis, as dysbiosis, or imbalances in the microbiota, can lead to chronic inflammation, which promotes carcinogenesis through the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Pathogens like <i>Porphyromonas gingivalis</i> and <i>Fusobacterium nucleatum</i> have, hence, been implicated in OSCC-driven tumor progression, as they induce inflammation, activate oncogenic pathways, and modulate immune responses. In this review, we discuss how the interplay between immunosuppression and microbiome-driven inflammation creates a tumor-promoting environment in OSCC, leading to treatment resistance and poor patient outcomes, and explore the potential therapeutic implication of a better understanding of OSCC etiology and molecular changes.
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spelling doaj-art-010ec27a7fc04745b02bcb3e386578d52025-08-20T03:47:48ZengMDPI AGBiomolecules2218-273X2025-04-0115562110.3390/biom15050621Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature ReviewLaertty Garcia de Sousa Cabral0Isabela Mancini Martins1Ellen Paim de Abreu Paulo2Karina Torres Pomini3Jean-Luc Poyet4Durvanei Augusto Maria5Faculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo 05508-220, SP, BrazilLaboratory of Development and Innovation, Butantan Institute, Sao Paulo 05585-000, SP, BrazilFaculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo 05508-220, SP, BrazilDepartment of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília 17525-902, SP, BrazilINSERM UMRS1342—CNRS EMR8000, Institut De Recherche Saint-Louis, Hôpital Saint-Louis, 75010 Paris, FranceFaculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo 05508-220, SP, BrazilThe tumor microenvironment (TME) plays a crucial role in the development, progression, and metastasis of oral squamous cell carcinoma (OSCC). The TME comprises various cellular and acellular components, including immune cells, stromal cells, cytokines, extracellular matrix, and the oral microbiome, all of which dynamically interact with tumor cells to influence their behavior. Immunosuppression is a key feature of the OSCC TME, with regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) contributing to an environment that allows tumor cells to evade immune surveillance and supports angiogenesis. The oral microbiome also plays a pivotal role in OSCC pathogenesis, as dysbiosis, or imbalances in the microbiota, can lead to chronic inflammation, which promotes carcinogenesis through the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Pathogens like <i>Porphyromonas gingivalis</i> and <i>Fusobacterium nucleatum</i> have, hence, been implicated in OSCC-driven tumor progression, as they induce inflammation, activate oncogenic pathways, and modulate immune responses. In this review, we discuss how the interplay between immunosuppression and microbiome-driven inflammation creates a tumor-promoting environment in OSCC, leading to treatment resistance and poor patient outcomes, and explore the potential therapeutic implication of a better understanding of OSCC etiology and molecular changes.https://www.mdpi.com/2218-273X/15/5/621oral squamous cell carcinomatumor microenvironmenttargeted therapies
spellingShingle Laertty Garcia de Sousa Cabral
Isabela Mancini Martins
Ellen Paim de Abreu Paulo
Karina Torres Pomini
Jean-Luc Poyet
Durvanei Augusto Maria
Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review
Biomolecules
oral squamous cell carcinoma
tumor microenvironment
targeted therapies
title Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review
title_full Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review
title_fullStr Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review
title_full_unstemmed Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review
title_short Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review
title_sort molecular mechanisms in the carcinogenesis of oral squamous cell carcinoma a literature review
topic oral squamous cell carcinoma
tumor microenvironment
targeted therapies
url https://www.mdpi.com/2218-273X/15/5/621
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