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    Emerging hyperthermia applications for pediatric oncology. Tydings Caitlin,Sharma Karun V,Kim AeRang,Yarmolenko Pavel S Advanced drug delivery reviews Local application of hyperthermia has a myriad of effects on the tumor microenvironment as well as the host's immune system. Ablative hyperthermia (typically > 55 °C) has been used both as monotherapy and adjuvant therapy, while mild hyperthermia treatment (39-45 °C) demonstrated efficacy as an adjuvant therapy through enhancement of both chemotherapy and radiation therapy. Clinical integration of hyperthermia has especially great potential in pediatric oncology, where current chemotherapy regimens have reached maximum tolerability and the young age of patients implies significant risks of late effects related to therapy. Furthermore, activation of both local and systemic immune response by hyperthermia suggests that hyperthermia treatments could be used to enhance the anticancer effects of immunotherapy. This review summarizes the state of current applications of hyperthermia in pediatric oncology and discusses the use of hyperthermia in the context of other available treatments and promising pre-clinical research. 10.1016/j.addr.2020.10.016
    PD-1 Blockade Boosts Radiofrequency Ablation-Elicited Adaptive Immune Responses against Tumor. Shi Liangrong,Chen Lujun,Wu Changping,Zhu Yibei,Xu Bin,Zheng Xiao,Sun Mingfen,Wen Wen,Dai Xichao,Yang Min,Lv Quansheng,Lu Binfeng,Jiang Jingting Clinical cancer research : an official journal of the American Association for Cancer Research PURPOSE:Radiofrequency ablation (RFA) has been shown to elicit tumor-specific T-cell immune responses, but is not sufficient to prevent cancer progression. Here, we investigated immune-suppressive mechanisms limiting the efficacy of RFA. EXPERIMENTAL DESIGN:We performed a retrospective case-controlled study on patients with synchronous colorectal cancer liver metastases who had received primary tumor resection with or without preoperative RFA for liver metastases. Tumor-infiltrating T cells and tumoral PD-L1 expression in human colorectal cancer tissues were analyzed by immunohistochemistry. T-cell immune responses and PD-1/PD-L1 expression were also characterized in an RFA mouse model. In addition, the combined effect of RAF and PD-1 blockade was evaluated in the mouse RFA model. RESULTS:We found that RFA treatment of liver metastases increased not only T-cell infiltration, but also PD-L1 expression in primary human colorectal tumors. Using mouse tumor models, we demonstrated that RFA treatment of one tumor initially enhanced a strong T-cell-mediated immune response in tumor. Nevertheless, tumor quickly overcame the immune responses by inhibiting the function of CD8(+) and CD4(+) T cells, driving a shift to higher regulatory T-cell to Teff ratio, and upregulating PD-L1/PD-1 expression. Furthermore, we established that the combined therapy of RFA and anti-PD-1 antibodies significantly enhanced T-cell immune responses, resulting in stronger antitumor immunity and prolonged survival. CONCLUSIONS:The PD-L1-PD-1 axis plays a critical role in dampening RFA-induced antitumor immune responses, and this study provides a strong rationale for combining RFA and the PD-L1/PD-1 blockade in the clinical setting. 10.1158/1078-0432.CCR-15-1352
    Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma. Dumolard Lucile,Ghelfi Julien,Roth Gael,Decaens Thomas,Macek Jilkova Zuzana International journal of molecular sciences Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide and its incidence is rising. Percutaneous locoregional therapies, such as radiofrequency ablation and microwave ablation, are widely used as curative treatment options for patients with small HCC, but their effectiveness remains restricted because of the associated high rate of recurrence, occurring in about 70% of patients at five years. These thermal ablation techniques have the particularity to induce immunomodulation by destroying tumours, although this is not sufficient to raise an effective antitumour immune response. Ablative therapies combined with immunotherapies could act synergistically to enhance antitumour immunity. This review aims to understand the different immune changes triggered by radiofrequency ablation and microwave ablation as well as the interest in using immunotherapies in combination with thermal ablation techniques as a tool for complementary immunomodulation. 10.3390/ijms21124398
    Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma: Current status. Chen Lumin,Sun Jihong,Yang Xiaoming Cancer letters Radiofrequency ablation (RFA) is widely accepted as a first-line interventional oncology approach for hepatocellular carcinoma (HCC) and has the advantages of high treatment efficacy and low complication risk. Local control rates equivalent to hepatic resection can be reached by RFA alone when treating small HCCs (<2 cm) in favorable locations. However, local tumor progression and recurrence rates with RFA monotherapy increase sharply when treating larger lesions (>3 cm). To address this clinical problem, recent efforts have focused on multimodel management of HCC by combining RFA with different techniques, including percutaneous ethanol injection, transarterial chemo-embolization, targeted molecular therapy, nanoparticle-mediated therapy, and immunotherapy. The combination strategy indeed leads to better outcomes in comparison to RFA alone. In this article, we review the current status of RFA-combined multimodal therapies in the management of HCC. 10.1016/j.canlet.2015.09.020
    Clinical and circulating biomarkers of survival and recurrence after radiofrequency ablation in patients with hepatocellular carcinoma. Canale Matteo,Ulivi Paola,Foschi Francesco Giuseppe,Scarpi Emanuela,De Matteis Serena,Donati Gabriele,Ercolani Giorgio,Scartozzi Mario,Faloppi Luca,Passardi Alessandro,Tamburini Emiliano,Valgiusti Martina,Marisi Giorgia,Frassineti Giovanni Luca,Casadei Gardini Andrea Critical reviews in oncology/hematology Radiofrequency ablation (RFA) is an effective local treatment for curative intent in patients with cirrhosis of the liver and hepatocellular carcinoma (HCC) with diameter <3 cm. Several meta-analyses have shown that RFA and surgical resection are comparable in terms of their impact on overall survival. The only clinical data available on markers that are predictive of recurrence and survival after RFA treatment are based on retrospective observational studies. Prospective randomized trials are thus needed to further research in this area. In the present review we analyzed a number of clinical factors that are considered to predict recurrence or survival in HCC patients treated with RFA. We also discussed in detail the circulating biomarkers investigated to date, together with their potential to predict prognosis and recurrence after RFA therapy. Overall survival rates of patients with HCC are significantly affected by liver function, defined as Child-Pugh class, high baseline serum alpha-fetoprotein levels, and the presence of portosystemic collaterals. However, the development of local tumor progression does not significantly affect overall survival. This result is achieved by the effective therapies in patients who relapse after treatment with RFA. For this reason there is an urgent need to identify new circulating biomarkers. 10.1016/j.critrevonc.2018.06.017