Melanoma-released exosomes directly activate the mitochondrial apoptotic pathway of CD4+ T cells through their microRNA cargo

Zhou, Ji; Yang, Yi; Wang, Wenwen; Zhang, Yuan; Chen, Zhengrong; Hao, Chuangli; Zhang, Jinping

doi:10.1016/j.yexcr.2018.08.030

Cited by 50 publications

(41 citation statements)

References 40 publications

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“…Further investigation found that the cancer-derived exosomes extraordinarily increased pro-apoptotic proteins (e.g., caspase-3/7/ 9) and decreased anti-apoptotic proteins (e.g., BCL-2/ xL and MCL-1) in CD4 + T cells [125]. In silico analysis indicated that a group of cancer-derived exosomal miRNAs such as miR-690 might contribute to this mitochondrial apoptosis of T cells [125]. Besides, Ye et al found that TW03 (nasopharyngeal carcinoma cell)-derived exosomes impaired the proliferation and differentiation of T cells [126].…”

Section: Cancer Cell-derived Mirnas Regulating Immune Evasion Via Exomentioning

confidence: 98%

“…3) [141]. [125]. When the release of exosome was inhibited, the abundance of TILs elevated and tumor growth was retarded [125].…”

Section: Cancer Cell-derived Mirnas Regulating Immune Evasion Via Exomentioning

confidence: 99%

“…[125]. When the release of exosome was inhibited, the abundance of TILs elevated and tumor growth was retarded [125]. Further investigation found that the cancer-derived exosomes extraordinarily increased pro-apoptotic proteins (e.g., caspase-3/7/ 9) and decreased anti-apoptotic proteins (e.g., BCL-2/ xL and MCL-1) in CD4 + T cells [125].…”

Section: Cancer Cell-derived Mirnas Regulating Immune Evasion Via Exomentioning

confidence: 99%

“…When the release of exosome was inhibited, the abundance of TILs elevated and tumor growth was retarded [125]. Further investigation found that the cancer-derived exosomes extraordinarily increased pro-apoptotic proteins (e.g., caspase-3/7/ 9) and decreased anti-apoptotic proteins (e.g., BCL-2/ xL and MCL-1) in CD4 + T cells [125]. In silico analysis indicated that a group of cancer-derived exosomal miRNAs such as miR-690 might contribute to this mitochondrial apoptosis of T cells [125].…”

Section: Cancer Cell-derived Mirnas Regulating Immune Evasion Via Exomentioning

confidence: 99%

“…Immunosuppressive [125] miR-24-3p NPC Immunosuppressive [126] miR-891a NPC Immunosuppressive [126] miR-106a-5p NPC Immunosuppressive [126] miR-20a-5p NPC Immunosuppressive [126] miR-1908 NPC Immunosuppressive [126] TAMs miR-222-3p EOC Immunosuppressive [127] miR-940 EOC Immunosuppressive [128] miR-21-3p EOC Immunosuppressive [129] miR-125b-5p EOC Immunosuppressive [129] miR-181d-5p EOC Immunosuppressive [129] miR-21 Head and neck cancer Immunosuppressive [130] miR-1246 Colon cancer Immunosuppressive [131] miR-16 Breast cancer Immunostimulatory [132] MDSCs miR-107 Gastric cancer Immunosuppressive [133] miR-21 OSCC Immunosuppressive [134] miR-21 Glioma Immunosuppressive [135] miR-10a Glioma Immunosuppressive [135] miR-29a Glioma Immunosuppressive [136] miR-92a Glioma Immunosuppressive [136] miR-155 CLL Immunosuppressive [137] CAFs miR-27a Gastric cancer Immunosuppressive [138] miR-1247-3p HCC Immunosuppressive [139] miR-21 HCC Immunosuppressive [140] NPC nasopharyngeal carcinoma, TAM tumor-associated macrophage, EOC epithelial ovarian cancer, MDSC myeloid-derived suppressor cell, OSCC oral squamous cell carcinoma, CLL chronic lymphocytic leukemia, CAF cancer-associated fibroblast, HCC hepatocellular carcinoma M2-like phenotype and suppressing the expression of M1 phenotype-associated markers [130]. Similarly, Cooks et al observed that cancer cells harboring TP53 mutation could reprogram neighboring TAMs into pro-tumor state via secreting miR-1246-enriched exosomes [131].…”

Section: Effector T Cells Mir-690 Melanomamentioning

confidence: 99%

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The role of cancer-derived microRNAs in cancer immune escape

et al. 2020

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During malignant transformation, accumulated somatic mutations endow cancer cells with increased invasiveness and immunogenicity. Under selective pressure, these highly immunogenic cancer cells develop multiple strategies to evade immune attack. It has been well established that cancer cells could downregulate the expression of major histocompatibility complex, acquire alterations in interferon pathway, and upregulate the activities of immune checkpoint pathways. Besides, cancer cells secret numerous cytokines, exosomes, and microvesicles to regulate the functions and abundances of components in the tumor microenvironment including immune effector cells and professional antigen presentation cells. As the vital determinant of post-transcriptional regulation, microRNAs (miRNAs) not only participate in cancer initiation and progression but also regulate anti-cancer immune response. For instance, some miRNAs affect cancer immune surveillance and immune escape by interfering the expression of immune attack-associated molecules. A growing body of evidence indicated that cancer-derived immune modulatory miRNAs might be promising targets to counteract cancer immune escape. In this review, we summarized the role of some miRNAs in cancer immune escape and discussed their potential clinical application as treatment targets.

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Section: Cancer Cell-derived Mirnas Regulating Immune Evasion Via Exomentioning

confidence: 98%

“…3) [141]. [125]. When the release of exosome was inhibited, the abundance of TILs elevated and tumor growth was retarded [125].…”

Section: Cancer Cell-derived Mirnas Regulating Immune Evasion Via Exomentioning

confidence: 99%

Section: Cancer Cell-derived Mirnas Regulating Immune Evasion Via Exomentioning

confidence: 99%

Section: Cancer Cell-derived Mirnas Regulating Immune Evasion Via Exomentioning

confidence: 99%

Section: Effector T Cells Mir-690 Melanomamentioning

confidence: 99%

See 3 more Smart Citations

The role of cancer-derived microRNAs in cancer immune escape

et al. 2020

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Biomimetic Immunosuppressive Exosomes that Inhibit Cytokine Storms Contribute to the Alleviation of Sepsis

Zhang

Chen

et al. 2022

Advanced Materials

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Sepsis is a disease characterized by multiple organ failure caused by immune hyperactivation and cytokine storms. Studies have shown that the incidence of sepsis in melanoma patients is substantially lower compared to the general population. It is also observed that experimental tumor‐bearing animals have high survival rates after sepsis induction, suggesting that tumors may suppress sepsis‐associated immune overactivation, thereby alleviating sepsis. Based on the above‐described findings, this work assesses whether tumor cells play an antisepsis role in mice through the secretion of exosomes. Analysis of exosome activity reveals that the induced exosomes (iExo) secreted by tumor cells following lipopolysaccharide (LPS) treatment improve sepsis to a greater extent than normal secretory exosomes. Further analysis reveals that iExo exert their protective effects mainly through seven key miRNAs. In vitro bionic simulation of exosomes is carried out using exosome mimics generated by loading the aforementioned microRNAs into hyaluronic acid–polyethylenimine nanoparticles. Exosome mimics at specific miRNA ratios alleviate sepsis in mice and cynomolgus monkeys, indicating that biomimetic simulation of tumor‐suppressive exosomes may represent a promising therapeutic method for the treatment of sepsis and cytokine‐storm‐related conditions.

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The effects of tumor‐derived exosomes on T‐cell function and efficacy of cancer immunotherapy

et al. 2021

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Tumor-derived exosomes (TEXs) are a class of extracellular vesicles which play an important role in the tumor microenvironment. These vesicles have multiple biological functions including promotion of cancer progression and reduction of anti-tumor immunity. Recently, interaction between TEXs and immune cells are of great interest in cell-based immunotherapy. Here, we review the effects of TEXs on the survival and functions of T cell subsets, as well as their clinical applications. Unraveling the immunoregulatory function of exosomes allows a better understanding of the molecular and cellular basis for cancer immunotherapy.

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Melanoma-released exosomes directly activate the mitochondrial apoptotic pathway of CD4+ T cells through their microRNA cargo

Cited by 50 publications

References 40 publications

The role of cancer-derived microRNAs in cancer immune escape

The role of cancer-derived microRNAs in cancer immune escape

Biomimetic Immunosuppressive Exosomes that Inhibit Cytokine Storms Contribute to the Alleviation of Sepsis

The effects of tumor‐derived exosomes on T‐cell function and efficacy of cancer immunotherapy

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