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Supplementation with Serum-Derived Extracellular Vesicles Reinforces Antitumor Immunity Induced by Cryo-Thermal Therapy.

ABSTRACT: Effective cancer therapies should reshape immunosuppression and trigger antitumor immunity. Previously, we developed a novel cryo-thermal therapy through applying local rapid cooling followed by rapid heating of tumor tissue. It could not only ablate local tumors, but also, subsequently, induce systemic long-term antitumor immunity. Hyperthermia can induce the release of extracellular vesicles (EVs) to stimulate antitumor immunity. We examine whether EVs are released after cryo-thermal therapy and whether they could improve the efficacy of cryo-thermal therapy in the 4T1 model. In this study, serum extracellular vesicles (sEVs) are isolated and characterized 3 h after cryo-thermal therapy of subcutaneous tumors. sEV phagocytosis is observed in vitro and in vivo by using laser confocal microscopy and flow cytometry. After cryo-thermal therapy, sEVs are administered to mice via the tail vein, and changes in immune cells are investigated by using flow cytometry. After cryo-thermal therapy, a large number of sEVs are released to the periphery carrying danger signals and tumor antigens, and these sEVs could be phagocytosed by peripheral blood monocytes and differentiated macrophages. After cryo-thermal therapy, supplementation with sEVs released after treatment promotes the differentiation of myeloid-derived suppressor cells (MDSCs), monocytes into macrophages and CD4+ T cells into the Th1 subtype, as well as prolonging the long-term survival of the 4T1 subcutaneous tumor-bearing mice. sEVs released after cryo-thermal tumor treatment could clinically serve as an adjuvant in subsequent cryo-thermal therapy to improve the therapeutic effects on malignant tumors.

SUBMITTER: Cen Y

PROVIDER: S-EPMC8539038 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Supplementation with Serum-Derived Extracellular Vesicles Reinforces Antitumor Immunity Induced by Cryo-Thermal Therapy.

Cen Yinuo Y Lou Yue Y Wang Junjun J Wang Shicheng S Peng Peng P Zhang Aili A Liu Ping P

International journal of molecular sciences 20211013 20

Effective cancer therapies should reshape immunosuppression and trigger antitumor immunity. Previously, we developed a novel cryo-thermal therapy through applying local rapid cooling followed by rapid heating of tumor tissue. It could not only ablate local tumors, but also, subsequently, induce systemic long-term antitumor immunity. Hyperthermia can induce the release of extracellular vesicles (EVs) to stimulate antitumor immunity. We examine whether EVs are released after cryo-thermal therapy a ...[more]

PMID: 34681680

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Project description:PurposeSABR has demonstrated clinical benefit in oligometastatic prostate cancer. However, the risk of developing new distant metastatic lesions remains high, and only a minority of patients experience durable progression-free response. Therefore, there is a critical need to identify which patients will benefit from SABR alone versus combination SABR and systemic agents. Herein we provide, to our knowledge, the first proof-of-concept of circulating prostate cancer-specific extracellular vesicles (PCEVs) as a noninvasive predictor of outcomes in oligometastatic castration-resistant prostate cancer (omCRPC) treated with SABR.Methods and materialsWe analyzed the levels and kinetics of PCEVs in the peripheral blood of 79 patients with omCRPC at baseline and days 1, 7, and 14 after SABR using nanoscale flow cytometry and compared with baseline values from cohorts with localized and widely metastatic prostate cancer. The association of omCRPC PCEV levels with oncological outcomes was determined with Cox regression models.ResultsLevels of PCEVs were highest in mCRPC followed by omCRPC and were lowest in localized prostate cancer. High PCEV levels at baseline predicted a shorter median time to distant recurrence (3.5 vs 6.6 months; P = .0087). After SABR, PCEV levels peaked on day 7, and median overall survival was significantly longer in patients with elevated PCEV levels (32.7 vs 27.6 months; P = .003). This suggests that pretreatment PCEV levels reflect tumor burden, whereas early changes in PCEV levels after treatment predict response to SABR. In contrast, radiomic features of 11C-choline positron emission tomography and computed tomography before and after SABR were not predictive of clinical outcomes. Interestingly, PCEV levels and peripheral tumor-reactive CD8 T cells (TTR; CD8+ CD11ahigh) were correlated.ConclusionsThis original study demonstrates that circulating PCEVs can serve as prognostic and predictive markers to SABR to identify patients with "true" omCRPC. In addition, it provides novel insights into the global crosstalk, mediated by PCEVs, between tumors and immune cells that leads to systemic suppression of immunity against CRPC. This work lays the foundation for future studies to investigate the underpinnings of metastatic progression and provide new therapeutic targets (eg, PCEVs) to improve SABR efficacy and clinical outcomes in treatment-resistant CRPC.

Dataset Information

Supplementation with Serum-Derived Extracellular Vesicles Reinforces Antitumor Immunity Induced by Cryo-Thermal Therapy.

Publications

Supplementation with Serum-Derived Extracellular Vesicles Reinforces Antitumor Immunity Induced by Cryo-Thermal Therapy.

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