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. 2025 Sep:168:107568.
doi: 10.1016/j.oraloncology.2025.107568. Epub 2025 Jul 29.

Prognostic impact of immune phenotype in oral squamous cell carcinoma

Michal Herman  1 , Jaroslav Michalek  2 , Richard Pink  1 , Katerina Kopecka  1 , Jana Zapletalova  3 , Sylva Hotarkova  4 , Michal Hendrych  4 , Zdenek Bednarik  4 , Michal Mozola  1 , Marketa Hermanova  5
Affiliations

Prognostic impact of immune phenotype in oral squamous cell carcinoma

Michal Herman et al. Oral Oncol. 2025 Sep.

Abstract

Background: In oral squamous cell carcinoma (OSCC), the current staging system fails to reliably identify high-risk patients, and potential biomarkers improving the prognostic, and predictive stratification of OSCC are sought. Due to the importance of tumor immune microenvironment in the development and progression of cancer, here we investigated the prognostic impact of immune phenotypes in OSCC.

Methods: The study included 119 OSCC patients treated by curative surgery. Based on the extent and spatial distribution of TILs in hematoxylin and eosin-staining, the tumors were classified as immune-excluded, immune-inflamed, and immune-desert. The prognostic significance and clinicopathological correlations of immune phenotypes were investigated, immunohistochemically detected PD-L1 expression levels were correlated with immune phenotypes.

Results: Immune-desert and immune-inflamed phenotypes significantly correlated with lymph node metastasis, higher stage, grade, and perineural invasion. A higher incidence of local recurrence was demonstrated in patients with immune-inflamed phenotype. PD-L1 expression levels correlated with immune phenotypes, with the highest expression levels in inflamed tumors. In Kaplan-Meier analysis, inferior survival rates were demonstrated in immune-desert and immune-inflamed OSCC (p < 0.0001). Cox regression showed an independent negative prognostic impact of both immune-inflamed and immune-desert phenotypes on disease-free (HR 5.327 and 4.256, respectively), disease-specific (HR 12.09 and 4.337), and overall survival (HR 4.502 and 4.300).

Conclusions: Our findings support that the histological evaluation of tumor immune phenotype might provide significant information on OSCC hazard discrimination, prognostication, and treatment decisions. The study identified immune-desert and immune-inflamed OSCC phenotypes associated with worse prognosis reflecting the lack of pre-existing anti-tumor immunity or immunosuppressive tumor immune microenvironment.

Keywords: Histopathology; Immune phenotype; Oral squamous cell carcinoma; PD-L1; Prognosis.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.