Cancer stem cells and tumor-associated macrophages: a roadmap for multitargeting strategies

Abstract

The idea that tumor initiation and progression are driven by a subset of cells endowed with stem-like properties was first described by Rudolf Virchow in 1855. 'Cancer stem cells', as they were termed more than a century later, represent a subset of tumor cells that are able to generate all tumorigenic and nontumorigenic cell types within the malignancy. Although their existence was hypothesized >150 years ago, it was only recently that stem-like cells started to be isolated from different neoplastic malignancies. Interestingly, Virchow, in suggesting a correlation between cancer and the inflammatory microenvironment, also paved the way for the 'Seed and Soil' theory proposed by Paget a few years later. Despite the time that has passed since these two important concepts were suggested, the relationships between Virchow's 'stem-like cells' and Paget's 'soil' are far from being fully understood. One emerging topic is the importance of a stem-like niche in modulating the biological properties of stem-like cancer cells and thus in affecting the response of the tumor to drugs. This review aims to summarize the recent molecular data concerning the multilayered relationship between cancer stem cells and tumor-associated macrophages that form a key component of the tumor microenvironment. We also discuss the therapeutic implications of targeting this synergistic interplay.

Role of tumor‐associated macrophages in human malignancies: friend or foe?

“…23 This niche is enriched in growth factors, cytokines, prostaglandins, and extracellular matrix components. Essential cellular players include TAMs and other immune cells, cancer-associated fibroblasts, mesenchymal stem cells, and endothelial cells.…”

Reprogramming of macrophages — new opportunities for therapeutic targeting

“…One major area of interest has been the deletion of macrophages by targeting macrophage specific cell surface receptors such as CSF1R, which has been recently reviewed [10] and will not be covered here. Similarly, there has been increasing interest in deleting or reprogramming tumor-associated macrophages, since it has become more and more clear that the presence of macrophages in many human cancers is associated with an unfavorable outcome (for excellent reviews see [1,8,9,[48][49][50][51]). …”

Effect of Coriolus versicolor glucan on the stimulation of cytokine production in sarcoma-180-bearing mice

“…Meanwhile, IL-4 serves a key role by stimulating the differentiation of naive T cells (Th0 cells) to Th2 cells (24). IL-6 is secreted by T cells and macrophages to enhance the immune reaction (25), to aid the differentiation and proliferation of T and B cells, and to advance the development of plasma cells from B cells (26). IL-10, also known as a human cytokine synthesis inhibitory factor, is an inhibitory cytokine that may hinder pathogen invasion and improve immunopathology (27).…”