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New insights into the role of the oral leukoplakia microenvironment in malignant transformation.

Wilfredo Alejandro González-Arriagada1,2,3, Gisela Canedo-Marroquin1,2, Daniela Adorno-Farías4

  • 1Facultad de Odontología, Universidad de los Andes, Santiago, Chile.

Frontiers in Oral Health
|March 7, 2024
PubMed
Summary

Oral leukoplakia, a precancerous lesion, involves complex microenvironment interactions. Understanding these immune and fibroblast roles is key to assessing malignant transformation risk and developing new therapies.

Keywords:
dysplasiafibroblastlymphocytemalignant transformationmicroenvironmentoral canceroral leukoplakiapremalignant

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Area of Science:

  • Oral pathology
  • Cancer biology
  • Immunology

Background:

  • Oral leukoplakia is the most common potentially malignant oral lesion.
  • Current risk assessment relies on dysplasia grading, but transformation risk prediction remains challenging.
  • Research is exploring alternative biomarkers, focusing on the tumor microenvironment.

Purpose of the Study:

  • To investigate the role of the oral microenvironment in leukoplakia progression.
  • To identify key cellular and molecular players in the dysplastic microenvironment.
  • To explore the microenvironment's potential for risk stratification and novel therapeutic strategies.

Main Methods:

  • Review of literature on oral leukoplakia microenvironment.
  • Analysis of immune cell infiltration, including T lymphocytes, regulatory T cells, macrophages, and Langerhans cells.
  • Evaluation of fibroblastic components, extracellular matrix, and associated factors like metalloproteinases and chemokines.

Main Results:

  • Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) are critical.
  • Immune aspects include T cell infiltration, immunosuppression, M2 macrophage polarization, and increased Langerhans cells.
  • Fibroblastic factors involve myofibroblast proliferation, altered matrix metalloproteinase/TIMP balance, and increased inflammatory mediators.

Conclusions:

  • The oral microenvironment significantly influences leukoplakia progression to carcinoma.
  • Understanding the interplay of immune cells and fibroblasts provides insights into malignant transformation.
  • Targeting microenvironmental components may offer new therapeutic avenues for potentially malignant oral lesions.