Cancer Stem Cells/Cancer Initiating Cells (CSCs/CICs) is a rare sub-population within a tumor that is responsible for tumor formation, progression and resistance to therapies. The interaction between CSCs/CICs and tumor microenvironment (TME) can sustain "stemness" properties and promote their survival and plasticity. This cross-talk is also pivotal in regulating and modulating CSC/CIC properties. This review will provide an overview of the mechanisms underlying the mutual interaction between CSCs/CICs and TME. Particular focus will be dedicated to the immunological profile of CSCs/CICs and its role in orchestrating cancer immunosurveillance. Moreover, the available immunotherapy strategies that can target CSCs/CICs and of their possible implementation will be discussed. Overall, the dissection of the mechanisms regulating the CSC/CIC-TME interaction is warranted to understand the plasticity and immunoregulatory properties of stem-like tumor cells and to achieve complete eradications of tumors through the optimization of immunotherapy.

Cancer stem cells or cancer-initiating cells (CSCs/CICs) represent a rare population within tumor lesions that are responsible for tumor formation, progression, and resistance to therapeutic interventions. These cells, due to their immunomodulating properties, can evade from immunosurveillance remaining as quiescent cells and might be responsible for resistance to immunotherapeutic treatments. Here the immunological properties of CSCs/CICs are summarized with special emphasis on the mechanisms underlying the impairment of T cell-mediated immune responses. A deep comprehensive genomic, molecular, and immunological characterization of CSCs/CICs needs to be further explored in order to design immunotherapy intervention that will allow the complete eradication of tumors, including the stem-like cellular components.