Resistance of cancer cells to CTL-mediated immunotherapy. Resistance to targeted anti-cancer therapeutics. Benjamin Bonavida, Salem Chouaib (Eds). Springer International Publishing Switzerland (2015)
Progress has been achieved in gaining the biological and immunological characterization of CSCs. Aberrantly expressed signaling pathways have been identified to be associated with CSCs and to confer their “stemness” properties and the ability to metastasize. In addition, these investigations have allowed the identification of markers that may be exploited to isolate ex vivo CSCs responsible for tumor initiation and propagation. Along this line, small agents are available to target CSCs that will be used soon for clinical studies.
Heterogeneity can be detected in CSCs isolated from different tumors depending on the genomic background and/or the histological origin, however, a common feature of these cells is their ability in evading cell-mediating immune responses. This characteristic is achieved by the expression and the activation in CSCs of a variety of immunomodulatory signaling pathways, thus leading to the impairment of cell-mediated immune responses specifically targeting CSCs (Fig. 1.2).
The immune privilege of CSCs can favor the survival of an immune-hidden reservoir of self-renewing cells that can warrant tumor propagation. Relevant implications are that the treatment with either a survival pathway inhibitor or differentiation-inducing small agents may be not sufficient for the complete CSC elimination. Therefore, the therapeutic combination of these agents with immunotherapy strategies is desirable. Novel immunotherapy strategies targeting CSCs should take into account the plasticity and heterogeneity of CSCs.
Further efforts are needed to fully dissect the relationship between CSCs and the innate/adaptive immune responses, however, the molecular identification of at least a few of the immunoregulatory molecules expressed by CSCs can enable to block these signaling pathways by the usage of appropriate immunomodulating agents (e.g. immune checkpoint blockade agents, inhibitory molecules).
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