Crosstalk Between Mesenchymal Stromal Cells and Tumor-Associated Macrophages in Gastric Cancer

Zheng, Ping; Li, Wei

doi:10.3389/fonc.2020.571516

Cited by 28 publications

(22 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study identified the TME-related gene PLXDC2 in a highstromal population and had a prognostic signature correlated to the CD163 M2 macrophages, further promoting EMT markers. Similar to the previous reporting that stromal EMT gene signature affects GC prognosis and immunotherapy responsiveness (Zheng and Li, 2020;Liu et al, 2021). The combined PLXDC2/EMT/M2 macrophages axis may affect GC outcome and immunotherapy responsiveness.…”

Section: Discussionsupporting

confidence: 89%

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

Guan

Wang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2’s correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.

show abstract

Section: Discussionsupporting

confidence: 89%

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

Guan

Wang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Immune surveillance is able to monitor, detect, and destroy cancer cells; however, as tumor progresses, cancer cells develop various mechanisms of immune evasion, leading to the development and the invasiveness of the tumor. A highly immunosuppressive microenvironment has been recently associated with the cross-talk between non-tumor-cell mesenchymal stromal cells (MSCs) and TAMs [ 121 ]. Namely, the differentiation from myeloid cells into M2-polarized macrophages, which, as mentioned before, are extremely immunosuppressive, seems to be mainly driven by exosomes produced by MSCs.…”

Section: Immunotherapy and Tme In Gastric Cancermentioning

confidence: 99%

“…Namely, the differentiation from myeloid cells into M2-polarized macrophages, which, as mentioned before, are extremely immunosuppressive, seems to be mainly driven by exosomes produced by MSCs. Moreover, the interactions between pro-inflammatory macrophages and MSCs, mainly mediated by CD54, can lead to an increase in the immunosuppressive activity of MSCs [ 121 ]. As such, the blockade of such a network between MSCs and TAMs may represent a new therapeutic target to exploit in order to restore immune tolerance and improve clinical outcomes in GC patients.…”

Section: Immunotherapy and Tme In Gastric Cancermentioning

confidence: 99%

Tumor-Associated Macrophages and Inflammatory Microenvironment in Gastric Cancer: Novel Translational Implications

Rihawi

Ricci

Rizzo

et al. 2021

IJMS

View full text Add to dashboard Cite

Gastric cancer (GC) represents the fifth most frequently diagnosed cancer worldwide, with a poor prognosis in patients with advanced disease despite many improvements in systemic treatments in the last decade. In fact, GC has shown resistance to several treatment options, and thus, notable efforts have been focused on the research and identification of novel therapeutic targets in this setting. The tumor microenvironment (TME) has emerged as a potential therapeutic target in several malignancies including GC, due to its pivotal role in cancer progression and drug resistance. Therefore, several agents and therapeutic strategies targeting the TME are currently under assessment in both preclinical and clinical studies. The present study provides an overview of available evidence of the inflammatory TME in GC, highlighting different types of tumor-associated cells and implications for future therapeutic strategies.

show abstract

“…Another source of EVs secretion is tumor-infiltrated Mesenchymal Stem Cells (MSC) derived from bone marrow for promoting regeneration, immune adaptation, and modulation of the TME [ 84 ]. In fact, a recent study showed that tumor-infiltrated MSCs secrete EVs for facilitating M2-like TAM polarization and promoting breast and gastric cancer (GC) progression [ 85 ].…”

Section: Heterogeneous Tam Polarizationmentioning

confidence: 99%

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

Wang

Yung

Ngan

et al. 2021

IJMS

101

View full text Add to dashboard Cite

Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget's “Seed and Soil” hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor β (TGFβ), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed.

show abstract

Crosstalk Between Mesenchymal Stromal Cells and Tumor-Associated Macrophages in Gastric Cancer

Cited by 28 publications

References 81 publications

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

Tumor-Associated Macrophages and Inflammatory Microenvironment in Gastric Cancer: Novel Translational Implications

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

Contact Info

Product

Resources

About