Abstract
Mounting evidence from the literature suggests the existence of a subpopulation of cancer stem cells (CSCs) in almost all types of human cancers. These CSCs possessing a self-renewal capacity inhabit primary tumors and are more defiant to standard antimitotic and molecularly targeted therapies which are used for eliminating actively proliferating and differentiated cancer cells. Clinical relevance of CSCs emerges from the fact that they are the root cause of therapy resistance, relapse, and metastasis. Earlier, surgery, chemotherapy, and radiotherapy were established as cancer treatment modalities, but recently, immunotherapy is also gaining importance in the management of various cancer patients, mostly those of the advanced stage. This review abridges potential off-target effects of inhibiting CSC self-renewal pathways on immune cells and some recent immunological studies specifically targeting CSCs on the basis of their antigen expression profile, even though molecular markers or antigens that have been described till date as expressed by cancer stem cells are not specifically expressed by these cells which is a major limitation to target CSCs. We propose that owing to CSC stemness property to mediate immunotherapy response, we can apply a combination therapy approach by targeting CSCs and tumor microenvironment (TME) along with conventional treatment strategies as an effective means to eradicate cancer cells.
Highlights
Cancer is a diverse heterogeneous disease which is characterized by phenotypically and functionally discrete subsets of cells
Accumulated evidences advocate that from the time when cancer stem cells (CSCs) were initially identified in human acute myeloid leukemia (AML), they have been isolated from many divergent malignancies, including cancers of the breast, prostate, colon, brain, pancreas, lung, liver, bladder, and ovary [4,5,6,7,8]
CSCs can be functionally distinguished from stem cells (SCs) by the fact that they exhibit a sluggish rate of cell division, amplified drug, and radiotherapy resistance and display an activation of detoxification pathways which forms the basis for their identification as well
Summary
Cancer is a diverse heterogeneous disease which is characterized by phenotypically and functionally discrete subsets of cells. Characterized by self-renewal and differentiation, these cells have been termed as cancer stem cells or tumor-initiating cells, and we have used CSCs to denote these cells throughout the review. CSCs are biologically similar to normal stem cells (SCs) [1, 2]. CSCs are characterized functionally by the intrinsic ability to initiate and long-term repopulate tumors with a recapitulation of the lineage/cellular heterogeneity seen in parental tumors [3]. Accumulated evidences advocate that from the time when CSCs were initially identified in human acute myeloid leukemia (AML), they have been isolated from many divergent malignancies, including cancers of the breast, prostate, colon, brain, pancreas, lung, liver, bladder, and ovary [4,5,6,7,8]. In order to design newer therapeutic approaches, we need a clearer understanding of the biology of these cells. e present review aims to Journal of Oncology determine the feasibility of immune targeting CSCs in solid tumors and highlights that some of the biological targetings of CSCs may be ambivalent by affecting immune responses
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