Characterization of immune cell infiltrate in tumor stroma and epithelial compartments in oral squamous cell carcinomas of Sudanese patients

Background 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. Methods Thirty-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. Results OSCC 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. Conclusions Despite 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.publishedVersio

Infective endocarditis: association between origin of causing bacteria and findings during oral infection screening

Background Oral streptococci represent the causing microorganism for infective endocarditis (IE) in many patients. The impact of oral infections is questioned, and it has been suggested that bacteraemia due to daily routines may play a bigger part in the aetiology of IE. The aim of this study was to examine the association between oral health and infective endocarditis caused by oral bacteria in comparison with bacteria of other origin than the oral cavity. Methods A retrospective study was conducted at Haukeland University Hospital from 2006- 2015. All consecutive adult patients admitted to hospital for treatment of IE and subjected to an oral focus screening including orthopantomogram, were included. The clinical, radiological and laboratory characteristics of the patients, collected during oral infectious focus screening, were analysed. Patient survival was calculated using Kaplan–Meier and mortality rates were compared using Cox-regression. Results A total of 208 patients were included, 77% (n = 161) male patients and 23% (n = 47) female, mean age was 58 years. A total of 67 (32%) had IE caused by viridans streptococci. No statistically significant correlation could be found between signs of oral infection and IE caused by viridans streptococci. The overall mortality at 30 days was 4.3% (95% CI: 1.6–7.0). There was no statistical difference in mortality between IE caused by viridans streptococci or S. aureus (HRR = 1.16, 95% CI: 0.57–2.37, p = 0.680). Conclusion The study indicates that the association between origin of the IE causing bacteria and findings during oral infection screening might be uncertain and may suggest that the benefit of screening and elimination of oral infections in patients admitted with IE might be overestimated. However, the results should be interpreted with caution and further studies are needed before any definite conclusions can be drawn.publishedVersio

Characterization of immune cell infiltrate in tumor stroma and epithelial compartments in oral squamous cell carcinomas of Sudanese patients

Background 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. Methods Thirty-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. Results OSCC 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. Conclusions Despite 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