Tumor-associated myeloid cells as guiding forces of cancer cell stemness

Abstract

Due to their ability to differentiate into various cell types and to support tissue regeneration, stem cells simultaneously became the holy grail of regenerative medicine and the evil obstacle in cancer therapy. Several studies have investigated niche-related conditions that favor stemness properties and increasingly emphasized their association with an inflammatory environment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are major orchestrators of cancer-related inflammation, able to dynamically express different polarized inflammatory programs that promote tumor outgrowth, including tumor angiogenesis, immunosuppression, tissue remodeling and metastasis formation. In addition, these myeloid populations support cancer cell stemness, favoring tumor maintenance and progression, as well as resistance to anticancer treatments. Here, we discuss inflammatory circuits and molecules expressed by TAMs and MDSCs as guiding forces of cancer cell stemness.

Granulocytic Myeloid‐Derived Suppressor Cells Promote the Stemness of Colorectal Cancer Cells through Exosomal S100A9

“…[12,31] The immunosuppressive roles of MDSCs are relatively well-understood in tumors. [12,31,34] It has been reported that MDSC enhances stem-like qualities in breast cancer cells. MDSC has been linked to cancer stemness.…”

The Cancer Stem Cell in Hepatocellular Carcinoma

“…Anti-inflammatory cells will be attracted to deal with the effect of pro-inflammatory innate immune cells (e.g., M1 macrophages and natural killer cells) and cytotoxic T cells. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) [53] enhance stemness and favor a pro-tumoral and pro-metastatic state by releasing cytokines (e.g., IL-6) that activate STAT3, ultimately inducing several stem-related pathways, EMT, and the expression of CSC markers, such as CD133 [54]. Underscoring the significance of the niche for the maintenance of CSCs, TAM depletion leads to a reduction in CSC numbers, tumor size and metastasis [55], while MDSC depletion increases the effect of cytotoxic T cells and reduces tumor growth [56].…”

Resveratrol ameliorates Lewis lung carcinoma‐bearing mice development, decreases granulocytic myeloid‐derived suppressor cell accumulation and impairs its suppressive ability

“…Although G‐MDSC and M‐MDSC could both impede T cell responses, the latter was more suppressive . Except for immunosuppressive effects on cancer development, more evidence showed that MDSC could accelerate the development of cancers by inducing autophagy, reprogramming metabolic status and supporting cancer cell stemness . It remains unclear whether RSV also modulated M‐MDSC in other cancer‐bearing mice models.…”

“…40 Except for immunosuppressive effects on cancer development, more evidence showed that MDSC could accelerate the development of cancers by inducing autophagy, reprogramming metabolic status and supporting cancer cell stemness. [41][42][43] It remains unclear whether RSV also modulated M-MDSC in other cancer-bearing mice models. Therefore, in future, we will consider the influence of RSV on M-MDSC in different cancer-bearing models.…”