The role of cancer stem cells in the modulation of anti-tumor immune responses.

Tumor lesions comprise multiple subpopulations of cells including those endowed with "stemness" properties. The latter cells are responsible of tumor initiation, metastasis formation, resistance to conventional therapies and disease recurrence. These relatively rare cells denominated cancer stem cells (CSCs) or cancer initiating cells (CICs) are defined based on self-renewing, multipotency and tumorigenicity. These cells through their immunomodulating features can evade from immunesurveillance, persisting in the form of quiescence and dormancy. They can drive the neoplastic growth and recurrence, even after long latency. Moreover, CSCs/CICs due to their ability to modulate and shape immune responses can represent the component of a tumor causing immunotherapy resistance in cancer patients. In this review a general overview of immunological properties of CSCs/CICs is provided, with a special focus on the mechanisms of modulation of T cell mediated responses. The need to further dissect the mechanisms regulating the immunological profile of CSCs/CICs and their interactions with immune cells and tumor microenvironment is discussed. An improved characterization of the immunological properties of CSCs/CICs will contribute to the rationale design of immunotherapeutic interventions which target these cells and may lead to the eradication of malignant diseases.