The Give-and-Take Interaction Between the Tumor Microenvironment and Immune Cells Regulating Tumor Progression and Repression

Abstract

A fundamental concern of the majority of cancer scientists is related to the identification of mechanisms involved in the evolution of neoplastic cells at the cellular and molecular level and how these processes are able to control cancer cells appearance and death. In addition to the genome contribution, such mechanisms involve reciprocal interactions between tumor cells and stromal cells within the tumor microenvironment (TME). Indeed, tumor cells survival and growth rely on dynamic properties controlling pro and anti-tumorigenic processes. The anti-tumorigenic function of the TME is mainly regulated by immune cells such as dendritic cells, natural killer cells, cytotoxic T cells and macrophages and normal fibroblasts. The pro-tumorigenic function is also mediated by other immune cells such as myeloid-derived suppressor cells, M2-tumor-associated macrophages (TAMs) and regulatory T (Treg) cells, as well as carcinoma-associated fibroblasts (CAFs), adipocytes (CAA) and endothelial cells. Several of these cells can show both, pro- and antitumorigenic activity. Here we highlight the importance of the reciprocal interactions between tumor cells and stromal cells in the self-centered behavior of cancer cells and how these complex cellular interactions control tumor progression and repression.

Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer

“…Finally, we normalized the expression profiles of 597 samples with complete follow-up information (Figure 1E). Previous references have reported the ability of CAFs to recruit immunosuppressive cells, so we performed immunofluorescence staining using immunofluorescence in patients with primary tumors and in patients with recurrent tumors (39). Interestingly, there was a recruitment of Treg cells (green) around the CAF cells (pink) in patients with primary tumors (Figure 2A), especially in the recurrent samples, where a larger number of Treg cells clustered to the prominent part of the CAF cells (Figure 2B).…”

EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis

“…These alterations consist of the recruitment of fibroblasts, migration of immune cells, stroma remodeling, and progression of tumor-specific vasculature [ 61 ]. The prognosis of cancer is correlated with immune cell infiltration and activation, thus the TME, which is composed of diverse infiltrating immune and stromal cells, may greatly impact therapy response and clinical outcome, in addition to playing a crucial role in cancer etiology and progression [ 62 , 63 ]. This study integrated multiple prediction methods to assess the association between EZH2 expression and the abundance of infiltrating immune cells in PCa in order to better determine the impact of the tumor immune microenvironment.…”

Basophils from allergy to cancer

“…Low percentages of basophils (0.4%) were located in the immune infiltrate of human non-small cell lung cancer (NSCLC) tumors (262). Basophils have been identified in the [263][264][265], which are often a prominent part of the immune cell landscape of the TME. However, in chronic inflammation, the exposure of basophils to certain cytokines, such as IL-33, may induce the polarization of lung macrophages to M2-like phenotype characterized by the expression of anti-inflammatory genes Clec7a, Arg1, Itgax.…”

“…It remains unclear what the exact function basophils mediate in the TME, yet emerging evidence points to their capacity to secrete IL-4 and IL-13 as playing a potential role. For example, mouse and human studies have shown that basophils, by secreting these cytokines, facilitate the development/expansion of M2-like monocytes/macrophages ( 227 , 263 – 265 ), which are often a prominent part of the immune cell landscape of the TME. However, in chronic inflammation, the exposure of basophils to certain cytokines, such as IL-33, may induce the polarization of lung macrophages to M2-like phenotype characterized by the expression of anti-inflammatory genes Clec7a, Arg1, Itgax .…”

“…Recent in vitro studies show that Gal-3, expressed by the A549 adenocarcinoma cell line (or EC-Gal-3), has the capacity to activate basophils to secrete copious amounts of IL-4/IL-13 ( 16 , 223 ). Both cytokines are known to promote M2-like macrophages, which are major players in the TME ( 227 , 263 – 265 ). IL-4-producing basophils have been identified in the TME of human pancreatic cancer, with mouse models indicating that this IL-4 promotes a Th2>Th1 response that is more conducive to tumorigenesis ( 80 ).…”