Deregulation of cytokine affecting oral neutrophil subsets in oral cancer.

The most prevalent form of leukocytes in human blood, neutrophils, is regarded as an essential part of the innate immune system and the body's 1st line of defense against foreign invaders. However, divergent opinions arise on the role of neutrophils in cancer, likely due to the occurrence of many neutrophil subsets. Several factors in the tumor microenvironment were found to modify the phenotype and function of neutrophils. Inhibitory cytokine production and recruitment of protumor immune cells to the tumor microenvironment are the reasons for immune suppression. Although some salivary cytokines were found to be increased in cancer patient's saliva, simultaneously, it was observed that those cytokines are high in other oral inflammatory conditions. So, it is challenging to distinguish at what level of expression those cytokines are involved in the neoplastic process. Therefore, the goal of this study is to provide a summary of the current information about the existence and presence of specific cytokines that impact cPMN and TAN and their potential activities in the context of healthy and cancer states so that we can relate to oPMN.

Understanding the functional relevance of oral neutrophils, phenotype and properties in OSCC.

Neutrophils are the predominant white blood cells (WBC) that are recruited to the sites of inflammation and infection. They are acknowledged to perform dual roles by promoting (pro-tumor) or by exhibiting anti-cancer properties (anti-tumor). Neutrophils are characterized based on the changes in phenotype and functional properties. To this context, circulating polymorphonuclear neutrophils (cPMN) and tumor-associated neutrophils (TANs) in cancer biology has been well explored but limited to oral polymorphonuclear neutrophils (oPMNs) in oral squamous cell carcinoma (OSCC). However, oPMNs are eminent in maintaining the healthy oral ecosystem by neutralizing microorganisms. Neutralization process enhances the expression of cell surface markers (CD11b, CD63, CD66, CD66b, CD66c, and CD66e) and inflammatory cytokines (TNF-α, IFN-γ, GM-CSF, and IL-8) and increases the recruitment of neutrophils. Along with the inflammation, it has been reported that CEACAM1 and chemerin also favors the infiltration of neutrophils to the cancer site. This indicates that oPMN might contribute to the aetiology of OSCC. The main objective of this review is to explore, the production and migration of oPMNs to the oral cavity, their phenotypes and possible role in OSCC.