Exosomes reveal the dual nature of radiotherapy in tumor immunology

Hu, Xinru; Qiu, Yuyue; Zeng, Xiaoping; Wang, Hongmei

doi:10.1111/cas.15314

Cited by 12 publications

(6 citation statements)

References 68 publications

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“…Exosomes take advantage of the targeting of related tumors to reach tumor tissues quickly and precisely, and then increase drug concentrations. The cytotoxic proteins contained in exosomes, such as perforin and Fas/FasL, can cause apoptosis of tumor cells, but do no harm to normal cells ( 103 , 204 ). Indeed, exosomes derived from NK cells are cytotoxic to melanoma cells but have no effect on normal cells ( 205 ).…”

Section: Roles Of Exosomes In the Tmementioning

confidence: 99%

Exosomes: A potential tool for immunotherapy of ovarian cancer

et al. 2023

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Ovarian cancer is a malignant tumor of the female reproductive system, with a very poor prognosis and high mortality rates. Chemotherapy and radiotherapy are the most common treatments for ovarian cancer, with unsatisfactory results. Exosomes are a subpopulation of extracellular vesicles, which have a diameter of approximately 30–100 nm and are secreted by many different types of cells in various body fluids. Exosomes are highly stable and are effective carriers of immunotherapeutic drugs. Recent studies have shown that exosomes are involved in various cellular responses in the tumor microenvironment, influencing the development and therapeutic efficacy of ovarian cancer, and exhibiting dual roles in inhibiting and promoting tumor development. Exosomes also contain a variety of genes related to ovarian cancer immunotherapy that could be potential biomarkers for ovarian cancer diagnosis and prognosis. Undoubtedly, exosomes have great therapeutic potential in the field of ovarian cancer immunotherapy. However, translation of this idea to the clinic has not occurred. Therefore, it is important to understand how exosomes could be used in ovarian cancer immunotherapy to regulate tumor progression. In this review, we summarize the biomarkers of exosomes in different body fluids related to immunotherapy in ovarian cancer and the potential mechanisms by which exosomes influence immunotherapeutic response. We also discuss the prospects for clinical application of exosome-based immunotherapy in ovarian cancer.

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Section: Roles Of Exosomes In the Tmementioning

confidence: 99%

Exosomes: A potential tool for immunotherapy of ovarian cancer

et al. 2023

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“…Exosomes derived from various cells serve an immunosuppressive or immunoenhancing role ( 18 ), and participate in carcinogenesis, proliferation and metastasis ( 19 ), thus playing distinct roles in the abscopal effect. Furthermore, there are alterations in exosome secretion following radiation ( 20 , 21 ). The subsequent sections discuss the mechanisms by which distinct cells produce exosomes after radiation to modify the abscopal effect.…”

Section: Immune Mechanism Of the Abscopal Effectmentioning

confidence: 99%

Mechanism of exosomes in the tumor microenvironment in the abscopal effect (Review)

et al. 2022

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Previously, the abscopal effect, which is an antitumor therapeutic effect on untreated tumor locations elsewhere in the body as a result of treatment of the targeted region, was rarely reported, and its mechanism remains unknown. Increasing evidence has shown that the immune system is implicated in the abscopal effect, and that combining immunotherapy and radiation can assist to improve its frequency. Understanding how different types of cells and cell-derived exosomes cause the abscopal effect in the tumor microenvironment (TME) is crucial to increasing the clinical occurrence of the abscopal effect in the TME. Contents 1. Introduction 2. Immune mechanism of the abscopal effect 3. Role of tumor cells 4. Roles of tumor-associated molecular patterns 5. Clinical application 6. Conclusions

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“…Studies have shown that exosomes induce immunosuppression and immune clearance by analyzing the relationship between exosomes and immunity. As a result, the prognosis of patients is not good 21 . In addition, extensive evidence indicates that the amount of exosomes secreted by tumor cells varies with cellular stress induced by anticancer therapy, leading to the transfer of drug‐resistance phenotypes between BC tumor cells 22,23 .…”

Section: Introductionmentioning

confidence: 99%

“…As a result, the prognosis of patients is not good. 21 In addition, extensive evidence indicates that the amount of exosomes secreted by tumor cells varies with cellular stress induced by anticancer therapy, leading to the transfer of drug‐resistance phenotypes between BC tumor cells. 22 , 23 In tumor progression and therapy, exosomes from BC cells are found to contribute to cancer cell proliferation, metastasis, angiogenesis, chemoresistance, and radioresistance, leading to metastasis of cancer cell lesions to other organs.…”

Section: Introductionmentioning

confidence: 99%

Low‐dose aspirin can inhibit exosomal release induced by radiotherapy in breast cancer and attenuate its inhibitory effect on NK cell proliferation

Wang,

Hu,

Chen

et al. 2023

Cancer Medicine

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BackgroundBreast cancer (BC) seriously threatens women's health. Aspirin plays a key role in the treatment and prognosis of BC.ObjectiveTo explore the effect of low‐dose aspirin on BC radiotherapy through the mechanism of exosomes and natural killer (NK) cells.MethodsBC cells were injected into the left chest wall to establish a BC model in nude mice. Tumor morphology and size were observed. Immunohistochemical staining for Ki‐67 was used to observe the proliferation of tumor cells. TUNEL was used to detect the apoptosis of cancer cells. Protein levels of exosomal biogenesis‐ and secretion‐related genes (Rab 11, Rab27a, Rab27b, CD63, and Alix) were detected by Western blot. Flow cytometry was used to detect apoptosis. Transwell assays were used to detect cell migration. A clonogenic assay was used to detect cell proliferation. Exosomes of BT549 and 4T1‐Luc cells were extracted and observed by electron microscopy. After the coculture of exosomes and NK cells, the activity of NK cells was detected by CCK‐8.ResultsThe protein expression of genes related to exosomal genesis and secretion (Rab 11, Rab27a, Rab27b, CD63, and Alix) in BT549 and 4T1‐Luc cells was upregulated under radiotherapy treatment. Low doses of aspirin inhibited exosome release from BT549 and 4T1‐Luc cells and alleviated the inhibitory effect of BC cell exosomes on NK cell proliferation. In addition, knocking down Rab27a reduced the protein levels of exosome‐related and secretion‐related genes in BC cells, further enhancing the promotive effect of aspirin on NK cell proliferation, while overexpressing Rab27a had the opposite effect. Aspirin was combined at a radiotherapeutic dose of 10 Gy to enhance the radiotherapy sensitivity of radiotherapy‐tolerant BC cells (BT549R and 4T1‐LucR). Animal experiments have also verified that aspirin can promote the killing effect of radiotherapy on cancer cells and significantly inhibit tumor growth.ConclusionLow doses of aspirin can inhibit the release of BC exosomes induced by radiotherapy and weaken their inhibition of NK cell proliferation, promoting radiotherapy resistance.

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Exosomes reveal the dual nature of radiotherapy in tumor immunology

Cited by 12 publications

References 68 publications

Exosomes: A potential tool for immunotherapy of ovarian cancer

Exosomes: A potential tool for immunotherapy of ovarian cancer

Mechanism of exosomes in the tumor microenvironment in the abscopal effect (Review)

Low‐dose aspirin can inhibit exosomal release induced by radiotherapy in breast cancer and attenuate its inhibitory effect on NK cell proliferation

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