Prognostic Value of the Immunohistochemical Detection of Cellular Components of the Tumor Microenvironment in Oral Squamous Cell Carcinoma: A Systematic Review

Abstract

This study aims to investigate the prognostic impact of cellular components of the tumor microenvironment (TME), analyzed through immunohistochemistry, in oral squamous cell carcinoma (OSCC). This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Web of Science, ScienceDirect, Scopus, and Google Scholar. After applying the study criteria, 59 articles were included, involving the analysis of cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. It was found that TME rich in α-SMA-positive CAFs, tumor-associated macrophages, and dendritic cells contribute to the invasion and progression of OSCC, resulting in a poorer prognosis. In contrast, the presence of high amounts of NK CD57⁺ cells, CD8⁺/CD45RO⁺ T cells, and PNAd⁺ endothelial cells are associated with anti-tumor immune responses in OSCC and improved survival rates. CD3⁺ and CD4⁺ T cells, Treg cells, B cells, and mast cells have shown little to no evidence of prognostic utility. Several stromal components of TME were found to have a strong impact on the aggressiveness of OSCC, reaffirming the potential use of these biomarkers as prognostic tools and therapeutic targets.

Keywords: immunohistochemistry; oral cancer; oral squamous cell carcinoma; prognosis; tumor microenvironment.

Figure 1

A flowchart of the literature search and selection criteria. The study followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Figure 2

The tumor microenvironment in OSCC highlighting the immunohistochemical markers of stromal cell components analyzed in this systematic review and their impact on patient survival.