Fibroblasts and macrophages cooperate to create a pro-tumorigenic and immune resistant environment via activation of TGF-β/IL-6 pathway in neuroblastoma

Louault, Kévin; Porras, Tania B.; Lee, Meng-Hua; Muthugounder, Sakunthala; Kennedy, Rebekah; Blavier, Laurence; Sarte, Emily; Fernández, G. Esteban; Yang, Fusheng; Pawel, Bruce; Shimada, Hiroyuki; Asgharzadeh, Shahab; DeClerck, Yves A.

doi:10.1080/2162402x.2022.2146860

Cited by 19 publications

(22 citation statements)

References 68 publications

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“…Zhang et al revealed that CAFs interacted with monocytes via the IL-8/CCR2 pathway, thereby inducing M2-type macrophages, which protected cancer cells from NK cell-mediated killing by reducing the cytotoxicity of NK cells [ 102 ]. Analogous results were reported by Louault et al [ 103 ], in which they confirmed that the suppressive effect on NK cells from CAF-TAM collaboration relied on TGF-β1. TGF-β signalling is an important pathway involved in tumour immune evasion [ 104 , 105 ].…”

Section: Macrophage–tumour Stroma Interactions Facilitate Immunosuppr...supporting

confidence: 89%

Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment

Cao,

Meng,

Zhang

et al. 2024

Cell Biosci

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Macrophages and tumour stroma cells account for the main cellular components in the tumour microenvironment (TME). Current advancements in single-cell analysis have revolutionized our understanding of macrophage diversity and macrophage–stroma interactions. Accordingly, this review describes new insight into tumour-associated macrophage (TAM) heterogeneity in terms of tumour type, phenotype, metabolism, and spatial distribution and presents the association between these factors and TAM functional states. Meanwhile, we focus on the immunomodulatory feature of TAMs and highlight the tumour-promoting effect of macrophage–tumour stroma interactions in the immunosuppressive TME. Finally, we summarize recent studies investigating macrophage-targeted therapy and discuss their therapeutic potential in improving immunotherapy by alleviating immunosuppression.

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Section: Macrophage–tumour Stroma Interactions Facilitate Immunosuppr...supporting

confidence: 89%

Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment

Cao,

Meng,

Zhang

et al. 2024

Cell Biosci

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“…In particular, we find occasionally that collagen accumulation is significantly reduced in the tumor tissues of collaborative therapy group (Figure g). It is widely recognized that extracellular matrix components in tumor tissues are mainly produced by cancer-associated fibroblasts (CAFs), which play crucial regulatory roles in the TME and are closely related to tumor progression and resistance to chemotherapy. , Concernedly, CAFs feature semblable characteristics with mesenchymal stromal cells (MSCs) in high-risk NB patients, and their presence typically indicates an unfavorable clinical prognosis. − MSCs preconditioned with conditional medium from NB cells exhibit heightened sensitivity to ferroptosis inducers due to the downregulation of the system X C – /GSH/GPX4 pathway . Therefore, the lethality of this strategy against CAFs was investigated.…”

Section: Resultsmentioning

confidence: 99%

Enzyme-Mediated Bioorthogonal Cascade Catalytic Reaction for Metabolism Intervention and Enhanced Ferroptosis on Neuroblastoma

Wang,

Li,

Cao

et al. 2024

J. Am. Chem. Soc.

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It remains a tremendous challenge to explore effective therapeutic modalities against neuroblastoma, a lethal cancer of the sympathetic nervous system with poor prognosis and disappointing treatment outcomes. Considering the limitations of conventional treatment modalities and the intrinsic vulnerability of neuroblastoma, we herein develop a pioneering sequential catalytic therapeutic system that utilizes lactate oxidase (LOx)/horseradish peroxidase (HRP)-loaded amorphous zinc metal−organic framework, named LOx/HRP-aZIF, in combination with a 3-indole-acetic acid (IAA) prodrug. On the basis of abnormal lactate accumulation that occurs in the tumor microenvironment, the cascade reaction of LOx and HRP consumes endogenous glutathione and a reduced form of nicotinamide adenine dinucleotide to achieve the first stage of killing cancer cells via antioxidative incapacitation and electron transport chain interference. Furthermore, the generation of reactive oxygen species induced by HRP and IAA through bioorthogonal catalysis promotes ferritin degradation and lipid peroxidation, ultimately provoking self-enhanced ferroptosis with positive feedback by initiating an endogenous Fenton reaction. This work highlights the superiority of the natural enzyme-dependent cascade and bioorthogonal catalytic reaction, offering a paradigm for synergistically enzyme-based metabolismferroptosis anticancer therapy.

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“…In neuroblastoma, TAMs collaborate with cancer-associated fibroblasts (CAFs) and mesenchymal stromal cells (MSC) to support tumor progression, especially in relapse patients. TAMs induce CAF proliferation [ 73 ], and MSCs/CAFs shield monocytes from apoptosis through in an IL-6-dependent manner [ 95 ]. The interactions of monocytes and MSC resulted in the significant upregulation of several pro-tumorigenic cytokines and chemokines, including TGF-β1, MCP-1, IL-6, IL-8, and IL-4.…”

Section: Myeloid Subpopulations In the Neuroblastoma Microenvironmentmentioning

confidence: 99%

Targeting the myeloid microenvironment in neuroblastoma

Stip,

Teeuwen,

Dierselhuis

et al. 2023

J Exp Clin Cancer Res

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Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid cells pose a challenge for the adaptive immune system to eliminate tumor cells, especially in high-risk neuroblastoma. This review first summarizes the pro- and anti-tumorigenic functions of myeloid cells, including granulocytes, monocytes, macrophages, and myeloid-derived suppressor cells (MDSC) during the development and progression of neuroblastoma. Secondly, we discuss how myeloid cells are engaged in the current treatment regimen and explore novel strategies to target these cells in neuroblastoma. These strategies include: (1) engaging myeloid cells as effector cells, (2) ablating myeloid cells or blocking the recruitment of myeloid cells to the tumor microenvironment and (3) reprogramming myeloid cells. Here we describe that despite their immunosuppressive traits, tumor-associated myeloid cells can still be engaged as effector cells, which is clear in anti-GD2 immunotherapy. However, their full potential is not yet reached, and myeloid cell engagement can be enhanced, for example by targeting the CD47/SIRPα axis. Though depletion of myeloid cells or blocking myeloid cell infiltration has been proven effective, this strategy also depletes possible effector cells for immunotherapy from the tumor microenvironment. Therefore, reprogramming of suppressive myeloid cells might be the optimal strategy, which reverses immunosuppressive traits, preserves myeloid cells as effectors of immunotherapy, and subsequently reactivates tumor-infiltrating T cells.

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Fibroblasts and macrophages cooperate to create a pro-tumorigenic and immune resistant environment via activation of TGF-β/IL-6 pathway in neuroblastoma

Cited by 19 publications

References 68 publications

Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment

Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment

Enzyme-Mediated Bioorthogonal Cascade Catalytic Reaction for Metabolism Intervention and Enhanced Ferroptosis on Neuroblastoma

Targeting the myeloid microenvironment in neuroblastoma

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