The current understanding of tumor-mediated immunosuppression in patients with solid tumors is to suppress the lymphocyte proliferation and interleukin-6 (IL-6) production via secreting prostaglandin E2 (PGE2) and transforming growth factor-ß2 (TGF- ß2). In this regard, cancer stem cells (CSCs) have gained attention in recent years. CSCs represent the subpopulation of tumor cells that demonstrate the ability of self-renewal and differentiation. CSCs are shown to play a crucial role in tumor proliferation, invasion, recurrence, therapeutic resistance, and immune evasion. Moreover, evidence strongly indicates that CSCs are strong mediators of immunosuppression of the specific T cell response and adaptive immune system. It is reported that CSCs express low major histocompatibility complex (MHC) and co-stimulatory molecules, thereby mediating defective antigen presentation mechanism and consequently leading to reduced antitumor immune response.
CSCs are shown to have several aberrantly active signaling pathways such as; NOTCH, Hedgehog (HH), WNT, MAPK, PI3K, EGFR, STAT3, VEGF, and BMP that regulate the self-renewal and differentiation. Intriguing evidence suggests that these active signaling pathways are key players of CSC-mediated immunosuppression mechanisms in the tumor microenvironment. STAT3 has been implicated in the suppression of macrophage activation and inhibiting dendritic cell-mediated activation of T cells via suppressing the expression of MHC II, IL-2, CD86, and CD80. A recent study showed WNT signaling was shown to be associated with defective MHC I molecules in CSCs isolated from surgical specimens. Furthermore, the inactivation of WNT signaling enhanced the cytotoxic T-lymphocyte-specific anti-tumor immune response. Thus, this evidence suggests that aberrantly active signaling in CSCs might be crucial in understanding the immune-suppression mechanism mediated by CSCs. Investigating the crosstalk and correlation between CSC-expressed signaling molecules and key tumor-infiltrating lymphocytes in the tumor microenvironment might open a new gateway towards solid tumor treatment.
The present Research Topic aims to update and summarize the recent findings elaborating the association between cancer stem cells mediated immuno-modulatory role in tumor microenvironment primarily focusing on:
• CSC mediated immunosuppression
• Immune evasion mechanisms
• Role of immuno-regulatory molecules
• Targeted therapies for CSCs
• CSCs and immunotherapies
• Vaccines targeting CSCs
The current understanding of tumor-mediated immunosuppression in patients with solid tumors is to suppress the lymphocyte proliferation and interleukin-6 (IL-6) production via secreting prostaglandin E2 (PGE2) and transforming growth factor-ß2 (TGF- ß2). In this regard, cancer stem cells (CSCs) have gained attention in recent years. CSCs represent the subpopulation of tumor cells that demonstrate the ability of self-renewal and differentiation. CSCs are shown to play a crucial role in tumor proliferation, invasion, recurrence, therapeutic resistance, and immune evasion. Moreover, evidence strongly indicates that CSCs are strong mediators of immunosuppression of the specific T cell response and adaptive immune system. It is reported that CSCs express low major histocompatibility complex (MHC) and co-stimulatory molecules, thereby mediating defective antigen presentation mechanism and consequently leading to reduced antitumor immune response.
CSCs are shown to have several aberrantly active signaling pathways such as; NOTCH, Hedgehog (HH), WNT, MAPK, PI3K, EGFR, STAT3, VEGF, and BMP that regulate the self-renewal and differentiation. Intriguing evidence suggests that these active signaling pathways are key players of CSC-mediated immunosuppression mechanisms in the tumor microenvironment. STAT3 has been implicated in the suppression of macrophage activation and inhibiting dendritic cell-mediated activation of T cells via suppressing the expression of MHC II, IL-2, CD86, and CD80. A recent study showed WNT signaling was shown to be associated with defective MHC I molecules in CSCs isolated from surgical specimens. Furthermore, the inactivation of WNT signaling enhanced the cytotoxic T-lymphocyte-specific anti-tumor immune response. Thus, this evidence suggests that aberrantly active signaling in CSCs might be crucial in understanding the immune-suppression mechanism mediated by CSCs. Investigating the crosstalk and correlation between CSC-expressed signaling molecules and key tumor-infiltrating lymphocytes in the tumor microenvironment might open a new gateway towards solid tumor treatment.
The present Research Topic aims to update and summarize the recent findings elaborating the association between cancer stem cells mediated immuno-modulatory role in tumor microenvironment primarily focusing on:
• CSC mediated immunosuppression
• Immune evasion mechanisms
• Role of immuno-regulatory molecules
• Targeted therapies for CSCs
• CSCs and immunotherapies
• Vaccines targeting CSCs
