November 29, 2021

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Interaction between cancer stem cells and immune cells

Interaction between cancer stem cells and immune cells


Interaction between cancer stem cells and immune cells.  In 1994, Lapidot et al. found a CD34+/CD38- poorly differentiated cell subgroup in acute myeloid leukemia, which has stem cell-like self-renewal ability and powerful tumor initiation ability. It is an early cancer stem cell (CSCs) research . Cancer stem cells (CSCs) have the characteristics of initiating tumors, promoting metastasis, enhancing drug resistance, and self-renewal.

 

Interaction between cancer stem cells and immune cells

More and more studies have confirmed the interaction of CSCs with immune cells in the tumor microenvironment, including the effects of CSCs on tumor-associated macrophages, myeloid-derived suppressor cells and T cells, and the role of these immune cells in maintaining the stem cell properties of CSCs and their The importance of survival niche.

Interaction between cancer stem cells and immune cells
CSC stem cell regulation mechanism and its contribution to tumor markers


Cancer stem cells and tumor-associated macrophages

It is known that various cells (including CSCs) in TME secrete cytokines and chemokines, and recruit and polarize tumor-associated macrophages (TAMs). These TAMs were derived from bone marrow macrophages (BMDMs) and macrophages residing in local tissues (such as microglia in the brain, Kupffer cells in the liver, and alveolar macrophages in the lung). These macrophages Derived from stem cells and progenitor cells in embryonic tissues.

Interaction between cancer stem cells and immune cells

Chemokines produced by cancer stem cells help cancer stem cells recruit macrophages. In addition, the cytokines produced by cancer stem cells induce macrophage polarization through corresponding signal pathways.

Interaction between cancer stem cells and immune cells

 

 

TAMs induce cancer stem cells

TAMs can support the stem cell nature of CSCs and the niche of CSCs. Niche is particularly important in maintaining CSCs’ self-renewal, reproductive potential and tumor initiation. This supportive microenvironment is composed of cancer cells, immune cells, mesenchymal stem cells (MSCs), fibroblasts, endothelial cells and extracellular matrix (ECM).


Stromal cell paracrine factors play a prominent role in promoting the dryness of CSCs in the niche. For example, in breast and colon cancer, MSCs secrete prostaglandin E2 (PGE2), IL-6, IL-8 and CXCL1. Fibroblasts secrete POSTN. TAMs produce factors that allow differentiated cancer cells to acquire CSCs-like characteristics.

 

 

CSCs and MDSCs interact

MDSCs include polymorphic nuclei (PMN-MDSC) and mononuclear (M-MDSC) subgroups. Among all MDSCs, PMN-MDSCs account for more than 80%, and M-MDSCs can differentiate into TAMS. MDSCs are produced in bone marrow and are recruited into tumors by tumor-derived chemokines (such as CCL2 and CCL5). Similar to TAMs, MDSCs play an important role in regulating tumor angiogenesis, growth, metastasis and immunosuppression. More and more evidences have also revealed the symbiotic interaction between CSCs and MDSCs in TME. CSCs secrete soluble factors and exosomes to promote the infiltration, expansion and activation of MDSCs. Once MDSCs penetrate into TME, they can promote the dryness of CSC through different mechanisms.

Interaction between cancer stem cells and immune cells

 

 

CSCs and T cells interact

As shown in the figure below, CSCs and T cells can interact directly. CSCs release inhibitory cytokines such as TGF-β and exosomes inhibit T cells, and T cells release TNF-a and IFN-γ and other effectors against CSCs. CSCs can also inhibit T cell function through suppressor cells M2-TAM, MDSCs and Treg.

The following table is: the cytokines produced by different cancer CSCs and their target immune cells, as well as the main effect factors produced by T cells.

Cancer stem cells create an ecological niche for themselves in the tumor microenvironment to maintain their own survival and development. To improve the effect of tumor immunotherapy, destroying the niche of tumor stem cells is a direction.

 

(source:internet, reference only)


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