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. 2023 May 10;15(10):2688.
doi: 10.3390/cancers15102688.

OSCC in Never-Smokers and Never-Drinkers Is Associated with Increased Expression of Tumor-Infiltrating Lymphocytes and Better Survival

Mathias Fiedler  1 , Alisa Off  1   2 , Jonas Eichberger  1 , Steffen Spoerl  1 , Johannes G Schuderer  1 , Juergen Taxis  1 , Richard J Bauer  1   3 , Stephan Schreml  4 , Torsten E Reichert  1 , Tobias Ettl  1 , Florian Weber  2
Affiliations

OSCC in Never-Smokers and Never-Drinkers Is Associated with Increased Expression of Tumor-Infiltrating Lymphocytes and Better Survival

Mathias Fiedler et al. Cancers (Basel). .

Abstract

The aim of this study was to investigate the clinical, histopathologic, and immunologic differences of oral squamous cell carcinoma of never-smokers/never-drinkers and smokers/drinkers. Immunohistochemical staining for CD4, CD8, FoxP3, CD1a, and p16 was performed in 131 oral squamous cell carcinomas from smokers/drinkers and never-smokers/never-drinkers. Associations of smoking/drinking status with clinicopathologic data, immunohistochemical antibody expression, and survival were examined. Oral squamous cell carcinoma in never-smokers/never-drinkers was associated with the female gender (p < 0.001). Never-smokers/never-drinkers were older at diagnosis than smokers/drinkers (p < 0.001). Never-smokers/never-drinkers had more tumors in the maxilla, mandible, and tongue (p < 0.001). Pre-existing oral potentially malignant disorders appeared to be more common in never-smokers/never-drinkers (p < 0.001). Perineural invasion was more common in smokers/drinkers (p = 0.039). Never-smoking/never-drinking was associated with better overall survival (p = 0.004) and disease-specific survival (p = 0.029). High CD4+ T cell infiltration was associated with never-smoking/never-drinking (p = 0.008). Never-smokers/never-drinkers also showed increased CD8+ T cell infiltration (p = 0.001) and increased FoxP3+ Treg infiltration (p = 0.023). Furthermore, the total group of tumor-infiltrating lymphocytes was associated with never smoking/never drinking (p = 0.005). To conclude oral squamous cell carcinoma of the never-smokers/never-drinkers appears to be a distinct type of tumor, as it appears to have unique clinical and pathologic features and a more immunogenic microenvironment.

Keywords: CD1a; CD4; CD8; FoxP3; never-drinker; never-smoker; oral squamous cell carcinoma; tumor-infiltrating lymphocytes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of biopsy specimens from patients with oral squamous cell carcinomas with p16 positivity (a), high CD4 expression (b), high CD8 expression (c), high Forkhead box protein 3 (FoxP3) expression (d), high CD1a expression (e), and corresponding HE staining (f) (magnification 400×).
Figure 2
Figure 2
The influence of smoking and drinking on overall survival (a) and disease-specific survival (b) of patients with oral squamous cell carcinoma.
Figure 3
Figure 3
The influence of CD4 (a), CD8 (b), overall T-cell infiltration (CD4+CD8) (c), and Forkhead box protein 3 (FoxP3) (d) on overall survival in oral squamous cell carcinoma.
See this image and copyright information in PMC

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