Abstract
Innate immune cells form an integrative component of the tumor microenvironment (TME), which can control or prevent tumor initiation and progression, due to the simultaneous processing of both anti- and pro-growth signals. This decision-making process is a consequence of gene expression changes, which are in part dependent on post-transcriptional regulatory mechanisms. In this context, microRNAs have been shown to regulate both recruitment and activation of specific tumor-associated immune cells in the TME. This review aims to describe the most important microRNAs that target cancer-related innate immune pathways. The role of exosomal microRNAs in tumor progression and microRNA-based therapeutic strategies are also discussed.
Highlights
Local immune response has emerged as key factor in the modulation of the multistep process of cancer progression
A paradigmatic example is represented by miR-155, which mediates the antitumor potential of myeloid cells in early stages of breast cancer carcinogenesis [87]. miR-155 knockdown in myeloid cells induces faster tumor growth, reduction of M1-macrophages and enrichment of pro-tumor cytokines within tumor milieu
A study published in 2013 by Hedge et al demonstrated that miR-690 maintains myeloid-derived suppressor cells (MDSCs) at their immature immunosuppressive state by targeting CEBP/α, a transcription factor involved in cell cycle progression and terminal differentiation of myeloid cells [135]
Summary
Local immune response has emerged as key factor in the modulation of the multistep process of cancer progression (reviewed in [1,2]). Evidence supporting the involvement of the immune system in the recognition and eradication of developing tumors was provided by in vivo experiments on immunodeficient mice, including Rag2−/− , IFNγ−/− or Prf−/− genetic backgrounds [9,10,11,12,13]. These studies showed higher incidence of spontaneous and carcinogen-induced solid tumors as well as an increased incidence of lymphomas [13]. In this review we will focus on the role of miRNAs as molecular determinants in tumor progression and macrophage-mediated immune surveillance
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