Tumor cells hijack macrophages via lactic acid.

Abstract

Macrophages are among the most abundant cells in the tumor stroma and can contribute to neoplastic growth, invasion and metastatic diffusion by translating instructive signals delivered by transformed cells. These signals comprise soluble factors such as chemokines and cytokines.1 In many cancers, tumor-associated macrophages (TAMs) are constantly recruited to the tumor environment by the CCL2 chemokine that attracts CCR2+ monocytes circulating in the blood.2 It is generally accepted that the tumor environment polarizes TAMs to express a set of genes common to M2-type macrophages, a specialized subset intervening in inflammation resolution, tissue remodeling and control of parasitic infections.1 These genes include the neoangiogenesis-promoter vascular endothelial growth factor (VEGF) and the L-arginine-metabolizing enzyme arginase (ARG). A recent paper by Colegio et al.3 in Nature opens a new scenario, showing that TAMs can ‘sense’ metabolic changes typical of the malignant state.