ABSTRACT
In the last 10 years, cancer stem cells have interested the scientific community because this small tumorigenic population is also associated with tumor progression in human patients and specific targeting of cancer stem cells could be a strategy to eradicate cancers currently resistant to conventional therapy. Clinical studies have recently demonstrated that adding immune therapy to chemotherapy has survival benefits in comparison with chemotherapy alone that can sensitize tumors to immune cell-mediated killing (e.g., increasing sensitivity of tumor cells to subsequent cytotoxicity by T cells via upregulation of death receptors DR5 and Fas). However, loss of MHC molecules is often observed in cancer cells, rendering tumor cells resistant to CD8 T-cell-mediated cytotoxicity. For this reason, we review the role of other T-cell subsets, such as γδ T and NK cells that are able to efficiently recognize and kill tumor cells and that could be used in passive or active immunotherapy in cancer stem cell eradication.
Subject(s)
Colonic Neoplasms/therapy , Immunotherapy/methods , Killer Cells, Natural/immunology , Neoplastic Stem Cells/immunology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , T-Lymphocyte Subsets/immunology , Humans , T-Lymphocytes/immunologyABSTRACT
BACKGROUND: Until few years ago, all neoplastic cells within a tumour were suggested to have tumorigenic capacity, but recent evidences hint to the possibility that such feature is confined to a subset of Cancer Initiating Cells (CICs), also called Cancer Stem Cells (CSCs). These cells are the reservoir of the heterogeneous populations of differentiated cancer cells constituting the tumour bulk. Mechanisms shared with somatic stem cells, such as quiescence, self-renewal ability, asymmetric division and multidrug resistance, allow to these cells to drive tumour growth and to evade conventional therapy. OBJECTIVE: Here, we give a brief overview on the origin of CICs, the mechanisms involved in chemoresistance and therapeutic implications. CONCLUSION: Current cancer treatments, based on the assumption that tumour cell population responds homogeneously, have been developed to eradicate proliferating cells. The new model of tumorigenesis entails significant therapeutic implications, in fact if a small fraction of CICs survives conventional therapy it may lead to recurrence after month or years of apparent remission. Selective targeting of CICs could eliminate the tumour from the root, overcoming the emergence of clones capable of evading traditional therapy and increasing overall disease free survival.
