WBC & THEIR ROLE IN TUMOR MICROENVIRONMENT (TME) OF ORAL SQUAMOUS CELL CARCINOMA-A REVIEW

Abstract

Oral premalignant lesions (OPLs) that affect approximately 4.5% of the world's population usually precede the occurrence of Oral squamous cell carcinoma. These lesions are now included in oral potentially malignant disorders (OPMD). Majority of OPLs regress, yet, up to 30% of them ultimately progress through increasingly grades of dysplasia &culminate as oral cancer. Therefore, OPLs represent an intermediate phase during the evolution of normal mucosa into malignant tumor, owing to their acquisition of a subset of the genomic alterations from those necessary to develop into Oral Squamous cell Carcinoma(OSCC).(1) In India OSCC is responsible for more than 20% of new malignancies diagnosed every year, being the most prevalent malignancy in the nation. There are several prognostic factors which help to evaluate the risk associated with the OSCC and serve as subsequent treatment guidelines. Increasing evidence has, so far, suggested that inammation may be linked to pathogenesis of oral cancer. Also, the tumor microenvironment is considered a crucial component in the understanding of the biologic behavior of a neoplasm. Leukocytosis is common in patients with progressive oral squamous cell carcinoma, is related with T-classication, lympho-vascular permeation, and recurrence or metastasis, &, therefore could decrease survival. Tumor-related leukocytosis results from hematopoietic colony-stimulating factors and inammatory cytokines from solid tumors. (2,4) One of the new most promising histopathological factor in prognostic evaluation of OSCC is, the density of tumour inltrating lymphocytes (TILs). Different subsets of lymphocytes have different or even opposing functions in the tumor microenvironment. (2,6,7) Neutrophils contribute to cancer progression or regression via multiple mechanisms, including the suppression of cytotoxic as well as helper Tcell responses and the stimulation of tumor angiogenesis.(8) B cells also act as antigen-presenting cells, promote differentiation of Th1 cells and Tcyt cells, and directly kill cancer cells through release of Granzyme B, thus, having a tumor suppressive role. (9) Inltrating eosinophils in the tumor microenvironment (TME), supply direct and indirect mitogenic growth mediators that stimulate proliferation of neoplastic cells, as well as educate other stromal cell types to induce paracrine and juxtacrine mitogenic signaling molecules to support neoplastic growth which also appears true for oral squamous cell carcinomas (OSCCs). (10) The plasmacytoid dendritic cells (pDC), are specically important in cancer immunity as, these cells have been identied in many solid malignant tumors, including those of head and neck & may play a key role in tumor occurrence and development.(9,12) Mast cells have a long life and form a heterogeneous population of cells that seem to have both a positive and negative regulatory effect on the immune system. MCs accumulate into tumor microenvironment by the help of tumor cell-released chemoattractants such as SCF or CCL15 and actively recruit cells of the innate immune system mainly neutrophils, macrophages, and eosinophils and cells of the acquired immune system (B and T cells) to orchestrate antitumor immune responses (13) In cancer tissues, the inltration of macrophages is signicantly increased. Macrophages are recruited to this edge by tumor-derived chemotactic agents and are a major inltrating cell type in the leading edge of a carcinoma.(16) OSCC are highly immunogenic tumors that are often characterized by abundant inltration of immune cells, however, their function & prognostic value vary. (19, 20)