Abstract
Cancer stem cells (CSCs) are subpopulations of undifferentiated cancer cells within the tumor bulk that are responsible for tumor initiation, recurrence and therapeutic resistance. The enhanced ability of CSCs to give rise to new tumors suggests potential roles of these cells in the evasion of immune surveillance. A growing body of evidence has described the interplay between CSCs and immune cells within the tumor microenvironment (TME). Recent data have shown the pivotal role of some major immune cells in driving the expansion of CSCs, which concurrently elicit evasion of the detection and destruction of various immune cells through a number of distinct mechanisms. Here, we will discuss the role of immune cells in driving the stemness of cancer cells and provide evidence of how CSCs evade immune surveillance by exerting their effects on tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Treg) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). The knowledge gained from the interaction between CSCs and various immune cells will provide insight into the mechanisms by which tumors evade immune surveillance. In conclusion, CSC-targeted immunotherapy emerges as a novel immunotherapy strategy against cancer by disrupting the interaction between immune cells and CSCs in the TME.
Highlights
Cancer stem cells (CSCs) are subsets of cancer cells enriched with stem cell-like characteristics, including self-renewal ability and multilineage differentiation (Bhatia and Kumar, 2016)
A substantial body of literature has extensively described the interactions of tumor bulks with the immune system; investigations have only begun to elucidate the relationship of CSCs and immune cells within the tumor microenvironment (TME), paving the way for the development of rational therapeutic strategies to explore CSCimmune dynamics
The capability of CSCs in tumor initiation in partly immunocompromised mice e.g., SCID or NOD/SCID mice (T, B cells defect but natural killer (NK) cells present) suggests that these cells are empowered with the definitive ability to evade immune detection and surveillance, whereas non-CSCs require a higher extent of deficiency in immune system for generating tumors in NSG mice (Tsuchiya and Shiota, 2021)
Summary
Cancer stem cells (CSCs) are subsets of cancer cells enriched with stem cell-like characteristics, including self-renewal ability and multilineage differentiation (Bhatia and Kumar, 2016). It has been proposed that CSCs have an intrinsic immunosuppressive program involving recruiting macrophages and driving them toward M2 polarization at the tumor site (Brissette et al, 2012) This ability of CSCs is commonly found in ovarian, glioblastoma, liver, breast and lung cancers through activating the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) pathways and cytokines such as interleukin (IL)-8 and IL-10 (Iliopoulos et al, 2009; Ginestier et al, 2010; Mitchem et al, 2013; Fang et al, 2014). Sox2+ cancer cells, via activation of nuclear factor of activated T-cells (NFAT), STAT3 and NF-κB, express chemokines CCL3 and ICAM-1 and recruit TAMs into the TME (Yang et al, 2013; Mou et al, 2015) These findings suggest that CSCs play an important role in TAM recruitment and M2 polarization by secreting macrophage chemoattractants. CSCs attract, re-educate, and put macrophages into their service to support primary tumor growth
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