Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

SIMPLE SUMMARY: This review provides a critical overview of the state of the art of the characterization of the immunological profile of a rare component of the tumors, denominated cancer stem cells (CSCs) or cancer initiating cells (CICs). These cells are endowed with the ability to form and propagate tumors and resistance to therapies, including the most innovative approaches. These investigations contribute to understanding the mechanisms regulating the interaction of CSCs/CICs with the immune system and identifying novel therapeutic approaches to render these cells visible and susceptible to immune responses. ABSTRACT: Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.