RESUMO
Objectives: The aim of the present study was to examine the immunoexpression of CD44, p16 and VEGF in oral squamous cell carcinoma (OSCC) and correlate them to clinicopathological parameters and survival outcomes in order to clarify their prognostic impact. Material and Methods: A total of 68 individuals with OSCC recruited between 2011 and 2015 from two referral centres were enrolled in the study. The samples were placed on silanized glass slides and subjected to immunohistochemistry using anti-p16, anti-CD44 and anti-VEGF antibodies. The H Score was used for p16 and VEGF, while CD44 was scored according to the percentage of stained cells. Chi-square tests and Fisher's exact probability tests were used to compare clinicopathological characteristics according to the immunohistochemical expression, while overall survival and disease-free survival were estimated and compared using the Kaplan-Meier method and log-rank test, respectively. For all hypothesis tests, the level of significance was set at P ≤ 0.05. Results: No correlation was observed between the expression of tumour VEGF, p16 and CD44, and the clinicopathological characteristics analysed. Patients with high stromal VEGF expression had better disease-free survival than patients with low VEGF expression (P = 0.023). Conclusion: In summary, P16, CD44 and tumour VEGF did not prove to be good prognostic biomarkers. Stromal VEGF expression is suggested to be a good candidate prognostic biomarker, although additional studies are needed.
RESUMO
Patients infected by Leishmania braziliensis develop debilitating skin lesions. The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known. Transcriptional profiling identified increased expression of ICRs including PD-1, PDL-1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4+ and CD8+ T cell subsets. Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls. The proportions PD1+, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments. Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-γ production, but not TNF-α secretion in response to L. braziliensis recall antigen challenge in vitro. While we previously showed a significant correlation between the accumulation of senescent CD8+CD45RA+CD27- T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology. Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood. Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis.