Anticancer Drugs Cause Release of Exosomes with Heat Shock Proteins from Human Hepatocellular Carcinoma Cells That Elicit Effective Natural Killer Cell Antitumor Responses in Vitro

Lv, Li-Hong; Wan, Yun-Le; Lin, Yan; Zhang, Wei; Yang, Mingshi; Li, Guolin; Lin, Hui‐Ping; Shang, Chao; Chen, Yajin; Jun, Min

doi:10.1074/jbc.m112.340588

Cited by 409 publications

(355 citation statements)

References 47 publications

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“…127 More recently, Li-Hong et al demonstrated that exosomes derived from resistant anticancer drug-treated Hepatocellular Carcinoma (HCC) cells conferred a higher antitumor response by inducing HSP-specific NK cell responses in vitro and suggested HSP-bearing exosomes could be used as an efficient vaccine for hepatocellular carcinoma immunotherapy. 128 In apparent contrast with these results, we discovered an immunosuppressive function of HSP70 at the surface of exosomes. We have shown that all cancer cells analyzed so far have the ability to secrete exosomes with HSP70 in their membrane while normal "non cancerous" cells do not.…”

Section: Hsp-exosomes In Cancer Therapycontrasting

confidence: 81%

Exosomes in cancer theranostic: Diamonds in the rough

Cordonnier

Chanteloup

Isambert

et al. 2017

Cell Adhesion & Migration

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During the last 10 years, exosomes, which are small vesicles of 50-200 nm diameter of endosomal origin, have aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. Most cells can potentially release these nanovesicles that share with the parent cell a similar lipid bilayer with transmembrane proteins and a panel of enclosed soluble proteins such as heat shock proteins and genetic material, thus acting as potential nanoshuttles of biomarkers. Exosomes surface proteins allow their targeting and capture by recipient cells, while the exosomes' content can modify the physiological state of recipient cells. Tumor derived exosomes by interacting with other cells of the tumor microenvironment modulate tumor progression, angiogenic switch, metastasis, and immune escape. Targeting tumor-derived exosomes might be an interesting approach in cancer therapy. Furthermore, because a key issue to improve cancer patients' outcome relies on earlier cancer diagnosis (metastases, as opposed to the primary tumor, are responsible for most cancer deaths) exosomes have been put forward as promising biomarker candidates for cancer diagnosis and prognosis. This review summarizes the roles of exosomes in cancer and clinical interest, focusing on the importance of exosomal heat shock proteins (HSP). The challenges of clinical translation of HSPexosomes as therapeutic targets and biomarkers for early cancer detection are also discussed.

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Section: Hsp-exosomes In Cancer Therapycontrasting

confidence: 81%

Exosomes in cancer theranostic: Diamonds in the rough

Cordonnier

Chanteloup

Isambert

et al. 2017

Cell Adhesion & Migration

View full text Add to dashboard Cite

show abstract

“…In the context of hepatocellular carcinoma the release of heat-shock protein chaperones from EVs was shown to act as a decoy enabling a NK cell response to be directed away from tumor cells. In contrast, in resistant cell lines these HSP bearing EVs were upregulated 46 . Circulating EVs in breast cancer similarly enable tumor growth by downregulating NK cell activity 44 .…”

Section: Evs Set the Place And Time For Neo-angiogenesismentioning

confidence: 84%

Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

et al. 2016

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“…38 It has been reported that exosomes derived from anticancer drug-treated human HCC cells were rich in heat shock proteins, which could act as endogenous danger signals to stimulate NK cell-elicited antitumor responses in vitro. 39 However, more studies indicated that the cytotoxicity of NK cells was greatly impaired in tumor conditions.…”

Section: Polarization Of Tumor-promoting Macrophagesmentioning

confidence: 99%

The exosomes in tumor immunity

2015

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Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4 C and CD8 C T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4 C and CD8 C Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DCderived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.

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Anticancer Drugs Cause Release of Exosomes with Heat Shock Proteins from Human Hepatocellular Carcinoma Cells That Elicit Effective Natural Killer Cell Antitumor Responses in Vitro

Cited by 409 publications

References 47 publications

Exosomes in cancer theranostic: Diamonds in the rough

Exosomes in cancer theranostic: Diamonds in the rough

Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

The exosomes in tumor immunity

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