Biological role of the bidirectional interaction between epithelial-mesenchymal transition and PD-L1 expression in head and neck squamous cell carcinomas: A systematic review.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common head and neck malignant neoplasm. Despite progress in antineoplastic treatment for SCC, there are still high morbidity and mortality rates. Over the years, several tumor biomarkers have been suggested to predict the prognosis of patients with oral SCC. Studies point to a bidirectional association between the epithelial-mesenchymal transition (EMT) and the expression of PD-L1 with the aggressive biological behavior of the neoplastic cell. Thus, this systematic review aimed to explore the biological roles and mechanisms underlying the interaction between EMT and PD-L1 expression in head and neck SCC-derived cell lines. MATERIAL AND METHODS: An electronic search was performed in the PubMed/Medline, Web of Science, Science Direct, Scopus, Embase, and Cochrane Collaboration Library databases. Articles evaluating the in vitro relationship between EMT/PD-L1 interaction and the biological behavior of head and neck SCC cell lines were selected for this systematic review. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: After applying the previously established inclusion/exclusion criteria, 9 articles were included in the qualitative synthesis. The present systematic review suggests the existence of a bidirectional interaction between EMT and PD-L1 expression, which is related to alterations in the cell cycle, proliferation, apoptosis, and cell survival, affecting the migration and invasion ability of tumor cells. CONCLUSIONS: Combined targeting of the two pathways may be potentially effective for immunotherapy in head and neck SCC.

Myofibroblasts and increased angiogenesis contribute to periapical cystic injury containment and repair.

BACKGROUND: Myofibroblasts (MF) and angiogenesis are important factors in the development and expansion of cystic lesions, where these cells secrete growth factors and proteases, stimulating angiogenesis, matrix deposition and cell migration, affecting the growth of these periapicopathies. The present study aimed to evaluate the immunohistochemical expression of CD34 and α-SMA in radicular cysts (RC) and residual radicular cysts (RRC), with the purpose of contributing to a better understanding of the expansion and progression of these periapical lesions. MATERIAL AND METHODS: The present study os a descriptive, quantitative and comparative analysis of positive CD34 and α-SMA immunohistochemical expressions in 30 RC and 30 RRC specimens. α-SMA expression was evaluated in the fibrous capsule of the lesions, at 100x magnification below the epithelial lining. A total of 10 higher immunostaining fields were selected and subsequently, positive cells were quantified at 400x magnification, averaged per field. Regarding the angiogenic index, immuno-labeled microvessel counts for the anti-CD34 antibody were performed in 10 fields at 200x magnification. RESULTS: Statistically significant differences regarding α-SMA immunostaining were observed (p = 0.035), as well as a correlation between α-SMA versus CD34 (p = 0.004) in RRC. However, the angiogenic index obtained by immunostaining for CD34 indicated no statistical difference between lesions. Intense inflammatory infiltrates were predominant in RC, while mild and moderate degrees were more commonly observed in RRC (p <0.001). Intense inflammatory infiltrates were also more often noted in larger RRC (p = 0.041). Inflammatory infiltrates showed no significant correlation with α-SMA and CD34 immunostaining. CONCLUSIONS: The results indicate that the significant correlation found between the presence of MF and the angiogenic index are related to the repair process in RRC.

Extracellular vesicles from oral squamous carcinoma cells display pro- and anti-angiogenic properties.

BACKGROUND: A new intercellular communication mode established by neoplastic cells and tumor microenvironment components is based on extracellular vesicles (EVs). However, the biological effects of the EVs released by tumor cells on angiogenesis are not completely understood. Here, we aimed to understand the biological effects of EVs isolated from two cell lines of oral squamous cell carcinoma (OSCC) (SCC15 and HSC3) on endothelial cell tubulogenesis. METHODS: OSCC-derived EVs were isolated with a polymer-based precipitation method, quantified using nanoparticle tracking analysis and verified for EV markers by dot blot. Functional assays were performed to assess the angiogenic potential of the OSCC-derived EVs. RESULTS: The results showed that EVs derived from both cell lines displayed typical spherical-shaped morphology and expressed the EV markers CD63 and Annexin II. Although the average particle concentration and size were quite similar, SCC15-derived EVs promoted a pronounced tubular formation associated with significant migration and apoptosis rates of the endothelial cells, whereas EVs derived from HSC3 cells inhibited significantly endothelial cell tubulogenesis and proliferation. CONCLUSION: The findings of this study reveal that EVs derived from different OSCC cell lines by a polymer-based precipitation method promote pro- or anti-angiogenic effects.

Analysis of tryptase-positive mast cells and immunoexpression of MMP-9 and MMP-13 in periapical lesions.

AIM: To evaluate the immunoexpression of tryptase, MMP-9 and MMP-13 in periapical lesions, correlating them with the type of lesion, intensity of the inflammatory infiltrate and thickness of the epithelial lining. METHODOLOGY: Twenty periapical granulomas (PGs), twenty radicular cysts (RCs) and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using antitryptase, anti-MMP-9 and anti-MMP-13 antibodies. Immunoexpression of MMP-9 and MMP-13 was quantitatively evaluated both in the connective tissue of all lesions and in the epithelial lining of RCs and RRCs. Tryptase-positive mast cells were counted only in the connective tissue. The data were analysed using Kruskal-Wallis and Fisher's exact tests, as well as Spearman's correlation test (P < 0.05). RESULTS: In comparison with RCs and RRCs, PGs exhibited higher immunoexpression of tryptase, MMP-9 and MMP-13 (P = 0.002, P = < 0.001 and P < 0.001, respectively). In comparison with lesions with inflammatory infiltrates grades I and II, lesions with inflammatory infiltrate grade III had higher median percentages of MMP-13-positive cells (P = 0.003) and a tendency for higher expression of MMP-9 (P = 0.059). No significant difference was observed between the expression of the studied markers and epithelial thickness (P > 0.05). There were positive correlations between the number of tryptase-positive mast cells and the immunoexpression of MMP-9, as well as between the immunoexpression of MMP-9 and MMP-13. CONCLUSION: A larger number of tryptase-positive mast cells and greater enzymatic activity of MMP-9 and MMP-13 were found in PGs compared to RCs and RRCs. These findings are a characteristic of the dynamics of periapical diseases.

Immunoexpression of tryptase-positive mast cells in periapical granulomas and radicular cysts.

AIM: To evaluate and compare the immunoexpression of tryptase in samples of periapical granulomas (PGs) and radicular cysts (RCs) correlating it with the type of lesion, localization, intensity of the inflammatory infiltrate and thickness of the cystic epithelial lining, in order to gain insight into the phlogistic role of these cells in the lesions studied. METHODOLOGY: Twenty-five PGs and twenty-five RCs obtained from human teeth without endodontic treatment were submitted to morphological and immunohistochemical analysis using anti-tryptase antibody. Mast cells were identified and counted in three regions: intra-epithelial, central/superficial and deep portions. The data were analysed using the Mann-Whitney U-test (P < 0.05). RESULTS: In comparison with RCs, PGs exhibited higher immunoexpression of tryptase-positive mast cells located in both central/superficial and deep regions (P < 0.001 and P < 0.001, respectively). When considering the total number of mast cells and disregarding the location, the number of tryptase-positive mast cells increased gradually from RCs to PGs (P < 0.001). Lesions with inflammatory infiltrate grade III had greater number of tryptase-positive mast cells located in both central/superficial and deep regions than lesions with inflammatory infiltrates grade II (P = 0.045 and P = 0.025). When the location was ignored, the lesions with inflammatory infiltrate grade III also exhibited higher immunostaining of tryptase-positive mast cells (P = 0.01). CONCLUSIONS: Tryptase-positive mast cells were present in chronic periapical lesions in a larger number in periapical granulomas than in radicular cysts, in both central/superficial and deep regions.

Immunoexpression of MMPs-1, -2, and -9 in ameloblastoma and odontogenic adenomatoid tumor.

OBJECTIVE: The aim of this study was to evaluate and compare the expression of metalloproteinases-1, -2, and -9 in solid ameloblastoma and adenomatoid odontogenic tumor. METHODS: A total of 20 cases of solid ameloblastoma and 10 cases of adenomatoid odontogenic tumors were selected and immunohistochemically assessed. Metalloproteinases-1, -2, and -9 immunoexpression and their distribution pattern were noted and semiquantitatively scored. The scores obtained were statistically analyzed. RESULTS: Matrix metalloproteinase (MMP)-1 showed a predominant expression in both tumors and was found in stroma and parenchyma. For MMP-2, there was a varied expression, with 80% and 60% of immunoreactive tumor cells in ameloblastoma and adenomatoid odontogenic tumor respectively. Regarding stromal cells, 65% of ameloblastomas and 80% of adenomatoid odontogenic tumors showed positivity. There was immunoexpression of the MMP-9 in parenchymal and stromal cells in all cases of both tumors analyzed. A statistically significant difference in the expression of MMP-1 in relation to the expression of MMP-2 and -9 in ameloblastomas (P < 0.001) was observed. CONCLUSION: The results suggest that these metalloproteinases are related to growth and progression of tumors analyzed, and particularly in ameloblastoma, its highest aggressiveness may be, in part, a result of the active participation of the stromal cells and their products, such as the MMPs studied.

Immunohistochemical assessment of extracellular matrix components in syndrome and non-syndrome odontogenic keratocysts.

OBJECTIVE: Investigate the immunohistochemical distribution of fibronectin, tenascin, laminin and collagen IV in syndrome (SOKC) and non-syndrome odontogenic keratocysts (NSOKC). MATERIALS AND METHODS: Ten cases of SOKC and five of NSOKC were selected and streptoavidin-biotin technique was applied. The specimens were analyzed taking into account the following evaluation parameters: presence, continuity and thickness in the basement membrane and intensity, distribution and association with inflammatory cells in the cyst wall. RESULTS: Differences could be detected regarding tenascin, fibronectin and collagen IV between the SOKC and NSOKC. Tenascin was present in all cases along the basement membrane in SOKC and in five cases of NSOKC predominated negative areas. Furthermore, tenascin distribution was focal in the cyst wall in SOKC whereas in NSOKC it was diffuse. Concerning fibronectin, it was detected as a discontinuous band when present in SOCK and as a continuous band in NSOKC. Collagen IV was not present in the majority of the cases in SOKC. Negative areas for laminin predominated in the basement membrane in both groups. CONCLUSIONS: These findings show differences between the immunohistochemical expression of tenascin, fibronectin and collagen IV which might indicate a more aggressive biological behavior of SOKC as compared with NSOKC.