Cytometric assessment of the murine melanoma microenvironment in the course of experimental chemotherapy: analysis of inflammatory infiltrate and kinetics of tumor cell repopulation.

Abstract

Formerly comprehended as a group of altered cells in proliferation, today cancer is better understood as a microenvironment, in which the interactions between the cellular and molecular elements are determinative in tumor progression. As a result, the comprehension and prediction of a neoplasic event gain increasing complexity, as new components of this tumoral niche and their respective actions are identified. Among these constituents, and of great relevance, are the elements of innate immunity, which, as a series of experiments have shown, are involved in the aspect of immunological vigilance, as well as in mechanisms of tumor progression. The presence of an inflammatory infiltrate occurs in the majority of tumors and the composition of this infiltrate varies, in quantity as well as in quality, according to changes in the tumor microenvironment - for example, apoptosis and necrosis. Events like these, in turn, are frequent consequences of antitumoral therapeutics, for example chemotherapy. The tumoral repopulation observed in such therapies, which frequently makes treatment success difficult, depends, therefore, on the treatment's direct action on the tumor cell, as well as on its indirect action on the rest of the elements that comprise the tumor. This project aims to evaluate the murine melanoma microenvironment under the effect of treatment with the chemotherapy agents dacarbazine and cisplatin. The main objective is to develop a cytometric evaluation of the tumor, involving the characterization of the inflammatory infiltrate and a special focus on cellular death and proliferation, which will define the tumor repopulation kinetics.