Reciprocal Crosstalk Between the Tumor Microenvironment and Cancer Stem Cells

Cancer stem cells (CSCs), also referred to as cancer-initiating cells, are a small sub-group of cancer cells that exhibited increased capabilities of self-renewal, metastasis, and resistance to therapeutic drugs. Although the concept of CSCs is initially proposed as a hypothesis, evidence has been accumulated supporting the existence of CSCs and postulated CSCs have also been isolated from multiple tumor samples. CSCs reside in a particular microenvironment, which is usually immunosuppressive and consists of heterogeneous cell types, various cytokines and growth factors. The crosstalk between CSCs and the components in its residing immunosuppressive microenvironment plays a critical role for the maintenance and resistance development of CSCs. Recent research findings also revealed that CSCs and its surrounding cells together facilitated the formation of an immunosuppressive microenvironment where they resided.

CSCs are capable to remodel their residing microenvironment. It had been shown that CSCs can express certain factors to render the formation of an immunosuppressive microenvironment, in which key players for immune defense system including NK cells and cytotoxic CD8+ T cells are repressed. Recent findings also revealed that after oncogenic RAS initiation, abnormal reciprocal crosstalk between stem cells and their residing microenvironment was occurred and the benign-to-malignant transition of tumor microenvironment was subsequently triggered. Immune evasion of CSCs due to tumor microenvironment remodeling is usually a major cause for cancer treatment failure. Moreover, CSCs are highly heterogeneous and display great phenotypic plasticity. It had been shown that non-CSCs could be converted to CSCs-like cells. Multiple mechanisms, including environmental induction by cytokines and growth factors, exceptional expression of oncogenic transcription factor as well as epigenetic alterations were proposed for the explanation of non-CSCs acquiring CSCs properties. Resistance development due to the highly plastic behavior of CSCs usually predict a poor prognosis for cancer patients. Therefore, there is great need in revealing the associated microenvironment networks that are essential to the pathological characteristics of CSCs as well as finding ways to ameliorate the immunosuppressive microenvironment and accordingly sensitize CSCs to current therapeutic methods.

In this collection we mainly want to discuss the mutual impact of cancer stem cells and the tumor microenvironment. The discussion about countermeasures to tackle the key pathological features of cancer stem cells as well as the immunosuppressive microenvironment are also welcomed and will be included in this collection. We welcome the submission of Original Research, Review, Mini Review and perspective articles to cover the following, but not limited to, these specific questions:
• Mechanisms underpinning the crosstalk between cancer stem cells and tumor microenvironment
• Regulators related to the plasticity of non-CSCs switching to CSCs
• Factors related to the remodelling of tumor microenvironment
• Countermeasures to overcome the immunosuppressive tumor microenvironment and ameliorate the characteristics of cancer stem cells

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section.


Posted on

December 30, 2016