Cancer-associated fibroblasts: Vital suppressors of the immune response in the tumor microenvironment

Xuan, Xuenan; Niu, Yulan; Wang, Zi-Hao; Ye, Linlin; Peng, Wen-Bei; Zhou, Qiong

doi:10.1016/j.cytogfr.2022.07.006

Cited by 35 publications

(23 citation statements)

References 166 publications

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“…[ 34 ] Among these immune cells, cancer‐associated fibroblasts (CAFs) promote the metastasis, invasion, and migration of tumor cells by secreting various cytokines or EVs, and by inhibiting immune function. [ 35 ] Regulatory T cells (Tregs) are involved in promotion of tumor growth and development, leading to the development of metastatic tumors. [ 36 ] Macrophages, derived from circulatory monocytes, are an important source of TAMs in cancer microenvironments.…”

Section: Discussionmentioning

confidence: 99%

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

et al. 2023

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Lung cancer is a commonly diagnosed disease worldwide, with non-small cell lung cancers (NSCLCs) accounting for ≈ 85% of cases. Cigarette smoke is an environmental exposure promoting progression of NSCLC, but its role is poorly understood. This study reports that smoking-induced accumulation of M2-type tumor-associated macrophages (M2-TAMs) surrounding NSCLC tissues promotes malignancy. Specifically, extracellular vesicles (EVs) from cigarette smoke extract (CSE)-induced M2 macrophages promoted malignancy of NSCLC cells in vitro and in vivo. circEML4 in EVs from CSE-induced M2 macrophages is transported to NSCLC cells, where it reduced the distribution of ALKBH5 in the nucleus by interacting with Human AlkB homolog H5 (ALKBH5), resulting in elevated N6-methyladenosine (m6A) modifications. m6A-seq and RNA-seq revealed suppressor of cytokine signaling 2 (SOCS2)-mediated activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by regulating m6A modification of SOCS2 via ALKBH5. Down-regulation of circEML4 in EVs from CSE-induced M2 macrophages reversed EVs-enhanced tumorigenicity and metastasis in NSCLC cells. Furthermore, this study found that smoking patients showed an increase in circEML4-positive M2-TAMs. These results indicate that smoking-induced M2-TAMs via circEML4 in EVs promote the NSCLC progression through ALKBH5-regulated m6A modification of SOCS2. This study also reveals that circEML4 in EVs from TAMs acts as a diagnostic biomarker for NSCLC, especially for patients with smoking history.

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Section: Discussionmentioning

confidence: 99%

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

et al. 2023

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“…145 CAFs recruit suppressive cells (such as MDSCs) by secreting chemokines and cytokines, containing TGF-β, IL-6, C-X-C chemokine ligand 12 (CXCL12), and prostaglandin E2. 146 Besides, exosomes also participate in the communication of CAFs with other cells. 147 Tumor-secreted exosomes support the proliferation of cancer cells by reprogramming fibroblasts.…”

Section: Exosomes Regulate the Communication Between Cafs And Cancer ...mentioning

confidence: 99%

“…CAFs reshape the state of TME by crosstalk with cancer cells and other components, thereby contributing to the growth, metastasis and immune evasion of cancer treatment 145 . CAFs recruit suppressive cells (such as MDSCs) by secreting chemokines and cytokines, containing TGF‐β, IL‐6, C‐X‐C chemokine ligand 12 (CXCL12), and prostaglandin E2 146 …”

Section: Exosomes Regulate the Communications Between Tme And Cancer ...mentioning

confidence: 99%

The rising roles of exosomes in the tumor microenvironment reprogramming and cancer immunotherapy

Wu,

Han,

Dong

et al. 2024

MedComm

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Exosomes are indispensable for intercellular communications. Tumor microenvironment (TME) is the living environment of tumor cells, which is composed of various components, including immune cells. Based on TME, immunotherapy has been recently developed for eradicating cancer cells by reactivating antitumor effect of immune cells. The communications between tumor cells and TME are crucial for tumor development, metastasis, and drug resistance. Exosomes play an important role in mediating these communications and regulating the reprogramming of TME, which affects the sensitivity of immunotherapy. Therefore, it is imperative to investigate the role of exosomes in TME reprogramming and the impact of exosomes on immunotherapy. Here, we review the communication role of exosomes in regulating TME remodeling and the efficacy of immunotherapy, as well as summarize the underlying mechanisms. Furthermore, we also introduce the potential application of the artificially modified exosomes as the delivery systems of antitumor drugs. Further efforts in this field will provide new insights on the roles of exosomes in intercellular communications of TME and cancer progression, thus helping us to uncover effective strategies for cancer treatment.

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“…Numerous studies indicate that CAFs regulate immune infiltration and affect TIME composition, and influence the outcome of cancer immunotherapy (Barrett and Puré, 2020). CAFs control the infiltration and phenotypic alterations of immune cells as well as influence their spatial movement within the tumor to promote immune regulation (Xiang et al, 2022). For example, CAFs can induce immunosuppressive cells such as regulatory T cells (Treg cells) and myeloid-derived suppressor cells (MDSCs) by secreting various cytokines including CXCL12 and other effector molecules, suppressing the immune function of immune effector cells and cytotoxic T lymphocytes ultimately create a TIME for immune tolerance that is conducive to tumor progression (Mao et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

CAFs orchestrates tumor immune microenvironment—A new target in cancer therapy?

et al. 2023

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Cancer immunotherapy has opened a new landscape in cancer treatment, however, the poor specificity and resistance of most targeted therapeutics have limited their therapeutic efficacy. In recent years, the role of CAFs in immune regulation has been increasingly noted as more evidence has been uncovered regarding the link between cancer-associated fibroblasts (CAFs) and the evolutionary process of tumor progression. CAFs interact with immune cells to shape the tumor immune microenvironment (TIME) that favors malignant tumor progression, a crosstalk process that leads to the failure of cancer immunotherapies. In this review, we outline recent advances in the immunosuppressive function of CAFs, highlight the mechanisms of CAFs-immune cell interactions, and discuss current CAF-targeted therapeutic strategies for future study.

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Cancer-associated fibroblasts: Vital suppressors of the immune response in the tumor microenvironment

Cited by 35 publications

References 166 publications

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

The rising roles of exosomes in the tumor microenvironment reprogramming and cancer immunotherapy

CAFs orchestrates tumor immune microenvironment—A new target in cancer therapy?

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