Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient.
Objective:
Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics.
Methodology:
This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry.
Results:
There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells.
Conclusion:
Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.
Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 mg/mL Mat and 9.71 mg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.
113 Background: OSCC is a public health problem worldwide, mainly due to its advanced stage diagnosis. The late diagnosis is a nonsense problem in view of this neoplasia often begins as PML. Clinical, molecular and immunological factors have been associated with the cancerization process. Objective: evaluate clinical differences and immunohistochemistry expression of PD1, CD4 and CD8 in PML that transformed in OSCC (PML-OSCC) and PML that didn´t transformed in OSCC (PML-NOSSC). Methods: CD4, CD8 and PD1 immunohistochemistry studies were carried out on PML and OSCC samples of 11 patients with PML – OSCC and PML samples of 14 patients with PML-NOSCC. Statistical differences were analyzed between the two groups: PML-OSCC and PML-NOSCC. Results: Non-homogenous leukoplakia, tongue and lack of exposure to tobacco were associated with cancerization. PD1 strong immunoexpression were observed in 63.6% of PML and 90.9% of OSCC. There was no statistical difference CD4+ cells level in PML-OSCC and PML-NOSCC. A significant increase in CD8+ cells was noted in OSCC comparing with PML–OSCC (p = 0.05). CD8+ cells levels is higher in PML-NOSCC compared with PML-OSCC (p = 0.027). Conclusions: CD8+ cells infiltrate more PML-NOSCC than PML-OSCC. Carcinoma is more infiltrated by CD8+ cells than its associated premalignant lesion. The evolution of immune response from an immunosurveillance phase to editing, equilibrium, suppression and immuno-escape can be present in oral carcinogenesis process. Research Funding: FAPEMIG (Minas Gerais State Research Foundation).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.