Controlling role of Ly6Chigh Monocytes in breast cancer and C26 colon carcinoma

Abstract

Abstract Tumor microenvironment encompasses a wide variety of immune cells, which macrophages comprise the most dominant portion of them and thus are the major players in the connection between inflammation and cancer. These tumor-associated macrophages (TAMs) are derived from blood monocyte precursors and subsequently acquire distinct characteristics as a result of tumor micro-environmental cues. Monocytes are a heterogeneous population in the blood with an enormous plasticity whose fate and functions are dictated by the microenvironment. Therefore, the roles of specific Monocytes subsets in tumor progression and the molecular mechanisms for their impacts need to be elucidated. Ly6Chigh and Ly6Clow are two main different types of murine monocytes subsets that have been defined by distinct phenotypes and immunoregulatory functions. Recent data demonstrates that Ly6Chigh monocytes can recruit to inflammation loci while Ly6Clow monocytes are patrolling cells. We have developed a method to produce large number of Ly6Chigh monocytes in vitro. In our study we observed that, injection of these cells affects tumor progression in breast cancer and C26 colon carcinoma animal models. Activation of Ly6Clow monocytes by pro- or anti-inflammatory cytokines, results in displaying a genetic expression profile, corresponding to pro- or anti-inflammatory genes, respectively. Injection of pre- activated Ly6Clow monocytes toward pro- or anti-inflammatory polarization in C26 colon carcinoma showed that anti-inflammatory activated monocytes are more beneficial in delaying cancer cachexia. Increased knowledge of monocytes improves the chances to find therapies against a broad spectrum of diseases including cancer.