Targeting PI3K<i>γ</i>/AKT Pathway Remodels LC3‐Associated Phagocytosis Induced Immunosuppression After Radiofrequency Ablation

Zhang, Wenyue; Xu, Yanan; Xu, Xiaolin; Jiang, Qiongchao; Ruan, Jingliang; Wu, Ye; Zhou, Yingshi; Saw, Phei Er; Luo, Baoming

doi:10.1002/advs.202102182

Cited by 21 publications

(14 citation statements)

References 39 publications

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“…26 To evaluate the vascular changes in residual tumor after IRFA, we first establish IRFA models (Figure 1A). 27 We constructed 10 mouse models of hepatocellular carcinoma xenografts, which were randomly divided into control and IRFA groups (n = 5).…”

Section: Resultsmentioning

confidence: 99%

Bioactive Antiangiogenic Lipid Nanoparticles for Inhibiting Residual Tumor Growth after Insufficient Radiofrequency Ablation

Luo,

Tan,

Chen

et al. 2024

ACS Appl. Nano Mater.

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Radiofrequency ablation (RFA) is a safe and minimally invasive procedure and had been recommended as the first-line treatment for early stage hepatocellular carcinoma (HCC) by NCCN and CSCO guideline. However, it had been reported that insufficient radiofrequency ablation (IRFA) was the main cause of recurrence and metastasis for patients who underwent RFA. Angiogenesis in residual tumor after IRFA was one of the main reasons for tumor progression. Although a variety of antiangiogenesis drugs had been clinically applied, systemic side effects and treatment resistance may lead to poor prognosis. Herein, we constructed a bioactive lipid nanoparticle, on the basis of dipalmitoyl phosphatidic acid (DPPA LPs), to inhibit the growth of residual tumor via antiangiogenesis. We illustrated that angiogenetic factors (VEGFA and CUX1/FGF1 axis) were significantly upregulated in residual tumor after IRFA. DPPA LPs could significantly downregulate the expression of CUX1, FGF1, and VEGFA on tumor cells in both in vitro and in vivo experiments. While the residual tumor growth after IRFA was reduced through inhibition of neovascularization, which led to prolonged survival of tumor-bearing mice. Besides, DPPA LPs showed no significant in vivo toxicity for main organs. Thus, antiangiogenic DPPA LPs could be a robust, safe, and effective platform as a promising therapeutic modality for residual tumor after IRFA.

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Section: Resultsmentioning

confidence: 99%

Bioactive Antiangiogenic Lipid Nanoparticles for Inhibiting Residual Tumor Growth after Insufficient Radiofrequency Ablation

Luo,

Tan,

Chen

et al. 2024

ACS Appl. Nano Mater.

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“…From the above reports, we can speculate that there is immunosuppression after cryoablation in some cases. At present, the mechanism of immunosuppression is not clear, but some studies have shown that it may be related to the ratio of necrosis and apoptosis and the excessive production of Treg ( 49 , 75 , 76 ). No danger signals will be released when the tumor tissue dies due to apoptosis, so the DC without antigen presentation will not mature.…”

Section: Cryoablation Results In Changes In Immune Functionmentioning

confidence: 99%

Progress in the cryoablation and cryoimmunotherapy for tumor

et al. 2023

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With the rapid advancement of imaging equipment and minimally invasive technology, cryoablation technology is being used more frequently in minimally invasive treatment of tumors, primarily for patients with early tumors who voluntarily consent to ablation as well as those with advanced tumors that cannot be surgically removed or cannot be tolerated. Cryoablation is more effective and secure for target lesions than other thermal ablation methods like microwave and radiofrequency ablation (RFA). The study also discovered that cryoablation, in addition to causing tumor tissue necrosis and apoptosis, can facilitate the release of tumor-derived autoantigens into the bloodstream and activate the host immune system to elicit beneficial anti-tumor immunological responses against primary. This may result in regression of the primary tumor and distant metastasis. The additional effect called “ Accompanying effects “. It is the basis of combined ablation and immunotherapy for tumor. At present, there is a lot of research on the mechanism of immune response induced by cryoablation. Trying to solve the question: how positively induce immune response. In this review, we focus on: 1. the immune effects induced by cryoablation. 2. the effect and mechanism of tumor immunotherapy combined with cryoablation. 3.The clinical research of this combination therapy in the treatment of tumors.

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“…In addition, Ji et al (2021) showed that RFA and TACE combined with postoperative autologous cytokine-induced killer (CIK) cell immunotherapy reinfusion have significant efficacy in the treatment of primary HCC. A preclinical study demonstrated that PI3Kγ inhibitors could enhance anti-PD-1 therapy for the treatment of residual tumors after IRFA ( Liu et al, 2022b ). However, though these studies provide a strong rationale for combining RFA and the immunotherapies in the clinical setting, the roles of HIF in this action are extremely scarce.…”

Section: Combination Therapies In the Management Of Early And Unresec...mentioning

confidence: 99%

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

Xiao

Liu

et al. 2023

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is one of the most common digestive malignancies. HCC It ranges as the fifth most common cause of cancer mortality worldwide. While The prognosis of metastatic or advanced HCC is still quite poor. Recently, locoregional treatment, especially local ablation therapies, plays an important role in the treatment of HCC. Radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation are the most common-used methods effective and feasible for treating HCC. However, the molecular mechanisms underlying the actions of ablation in the treatments for HCC and the HCC recurrence after ablation still are poorly understood. Hypoxia-inducible factor (HIF), the key gene switch for adaptive responses to hypoxia, has been found to play an essential role in the rapid aggressive recurrence of HCC after ablation treatment. In this review, we summarized the current evidence of the roles of HIF in the treatment of HCC with ablation. Fifteen relevant studies were included and further analyzed. Among them, three clinical studies suggested that HIF-1α might serve as a crucial role in the RAF treatment of HCC or the local recurrence of HCC after RFA. The remainder included experimental studies demonstrated that HIF-1, 2α might target the different molecules (e.g., BNIP3, CA-IX, and arginase-1) and signaling cascades (e.g., VEGFA/EphA2 pathway), constituting a complex network that promoted HCC invasion and metastasis after ablation. Currently, the inhibitors of HIF have been developed, providing important proof of targeting HIF for the prevention of HCC recurrence after IRFA and HIFU ablation. Further confirmation by prospective clinical and in-depth experimental studies is still warranted to illustrate the effects of HIF in HCC recurrence followed ablation treatment in the future.

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Targeting PI3Kγ/AKT Pathway Remodels LC3‐Associated Phagocytosis Induced Immunosuppression After Radiofrequency Ablation

Cited by 21 publications

References 39 publications

Bioactive Antiangiogenic Lipid Nanoparticles for Inhibiting Residual Tumor Growth after Insufficient Radiofrequency Ablation

Bioactive Antiangiogenic Lipid Nanoparticles for Inhibiting Residual Tumor Growth after Insufficient Radiofrequency Ablation

Progress in the cryoablation and cryoimmunotherapy for tumor

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

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