Background: IFN-gamma and natural killer (NK) cells have been considered the most effective cells in the combat of cancer, contributing to better prognosis and longer survival. The aim of the study was to analyze and correlate the CD 57 immunopositive NK cell-mediated Interferon-γ pathway in regulating immune mechanisms in Oral Squamous Cell Carcinoma. Materials and Methodology: The study sample was composed of a total of 40 cases of histopathologically confirmed cases of Oral Squamous cell carcinoma (OSCC). Clinical data such as age, gender, habit history, signs and symptoms, and TNM staging were obtained for each case. The biopsy specimens of the cases obtained were fixed with 10% neutral buffered formalin and processed and embedded in paraffin wax. 3-4 μ thick sections were taken for hematoxylin and eosin staining and immunohistochemistry procedure. A saliva sample was collected from each patient and stored at 20 degree Celsius for estimation of salivary interferon-gamma levels using the sandwich ELISA technique. Results: CD 57 NK cells quantitative assessment was significantly associated with tumor budding, cell nest size, the pattern of invasion, lymphocytic host response, NK cell morphology, Depth of invasion, and Tumor thickness. The ratio of CD 57 immunopositive NK cells to salivary IFN-γ levels showed a significant association with histopathological grades, tumor size, and lymph node status. Conclusion: Adoptive cellular transfer therapy with NK cells has been advocated in both experimental models and clinical trials in treating hematopoietic malignancies. The strategy is based on reviving the patient innate immune surveillance and control of tumor invasion by the infusion of activated NK cells. The IFN-gamma and NK cell infiltration in oral squamous cell carcinoma might show a distinctive tumor microenvironment with a favorable local cytotoxic immune response against neoplastic cells.

Background: Epithelial–mesenchymal transition (EMT) is a complex process, in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. Aim: The aim of the study was to ascertain the role of hypoxia-mediated signaling pathways influencing EMT and angiogenesis in progression of oral submucous fibrosis (OSMF). Materials and Methods: Evaluation of the immunoexpression of alpha-smooth muscle actin (α-SMA), E-cadherin, vimentin, and factor VIII receptor antigen in OSMF and oral squamous cell carcinoma (OSCC) arising from OSMF was done. Differences between the different variables were analyzed using ANOVA test and Pearson’s Chi-square test, and Mann–Whitney test was also calculated. Results: The mean α-SMA positive myofibroblasts increased from Group 1 (OSMF) to Group 2 (OSCC), especially those in the deeper connective tissue stroma. The mean labeling index of vimentin and mean vessel density immunoexpression was more in Group 2 (OSCC) as compared to Group 1 (OSMF). Mean α-SMA correlated negatively with E-cadherin expression and positively with vimentin and factor VIII immunoexpression. E-cadherin expression correlated negatively with factor VIII and positively with Vimentin expression. Conclusions: The molecular mechanisms responsible for the development of OSCC in patients with OSMF require unification of multiple progressive pathogenetic mechanisms involved in the progression of the disease.