Abstract
BackgroundTumor immune infiltrate has been explored in oral squamous cell carcinoma (OSCC), but studies on simultaneous characterization of multiple immune cell subtypes separately in stromal and intraepithelial tumor compartments are limited.ObjectivesWe aimed to investigate the immune cell infiltrate in OSCC by using immunohistochemistry (IHC) for a panel of inflammatory cells in stromal and epithelial tumor compartments for a better characterization of the tumors.MethodsThirty‐six OSCC lesions and nine normal oral mucosa (NOM) samples from patients attending Khartoum Dental Teaching Hospital, Sudan were investigated for presence of tumor infiltrating lymphocytes, tumor‐associated macrophages, tumor‐associated neutrophils, and PD‐L1 positive cells in the inflammatory infiltrate by single and double IHC. Digital quantitative analysis (Aperio Technologies Inc.) was performed separately for stromal and epithelial compartments.ResultsOSCC cases displayed a higher inflammatory infiltrate in the associated stroma, but not in the epithelial compartment when compared to NOM. The immunosuppressive type of inflammatory infiltrate, that is, T regulatory cells (FoxP3+ cells) was identified to be significantly higher in the epithelial compartment of tumors with advanced clinical state. An immunoscore developed by combining intraepithelial FoxP3+ and CD4+ cells was found significantly higher in lesions from elderly patients, localized at toombak dipping‐related sites, poorly differentiated OSCCs, or with loco‐regional lymph node spreading.ConclusionsDespite heavy immune cell infiltration in tumor‐associated stroma, the majority of OSCCs in this cohort displayed a low intraepithelial immune infiltration. An immunoscore based on combined CD4 and FoxP3 intraepithelial expression may serve as an indicator of advanced tumor progression and should be further investigated for its use as potential prognostic biomarker in OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral malignancies, with increasing incidence in developing countries (International Agency for Research on Cancer, 2006)
An immunoscore based on combined CD4 and FoxP3 intraepithelial expression may serve as an indicator of advanced tumor progression and should be further investigated for its use as potential prognostic biomarker in oral squamous cell carcinoma (OSCC)
One of the major findings of this study is that the inflammatory cell infiltration was more abundant in tumor-associated stroma than intraepithelial compartment, resulting in low stroma to epithelial
Summary
Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral malignancies, with increasing incidence in developing countries (International Agency for Research on Cancer, 2006). In Sudan, OSCC poses a high burden of disease, being characterized by its aggressive behavior and a trend towards increasing incidence, morbidity, and mortality rates (Saeed et al, 2014). Both genetic and environmental factors contribute to OSCC oncogenesis. Tumor immune infiltrate has been explored in oral squamous cell carcinoma (OSCC), but studies on simultaneous characterization of multiple immune cell subtypes separately in stromal and intraepithelial tumor compartments are limited. Objectives: We aimed to investigate the immune cell infiltrate in OSCC by using immunohistochemistry (IHC) for a panel of inflammatory cells in stromal and epithelial tumor compartments for a better characterization of the tumors. The immunosuppressive type of inflammatory infiltrate, that is, T regulatory cells (FoxP3+ cells) was identified to be significantly higher in the epithelial compartment of tumors with
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