Radiofrequency ablation in combination with an mTOR inhibitor restrains pancreatic cancer growth induced by intrinsic HSP70

Gao, Shanshan; Pu, Ning; Yin, Hanlin; Li, Junhao; Chen, Qiangda; Yang, Mei; Lou, Wenhui; Chen, Yi; Zhou, Guofeng; Li, Changyu; Li, Guoping; Yan, Zhenlin; Liu, Lingxiao; Yu, Jun; Wang, Xiaolin

doi:10.1177/1758835920953728

Cited by 11 publications

(14 citation statements)

References 49 publications

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“…If percutaneous RFA is feasible, it could avoid unnecessary laparotomy, thus reducing the risk of surgical complications as well as the time and costs of the treatment[ 46 ]. Moreover, while surgery involves an impaired immune response, enhanced immune system stimulation and immune response against the tumour have been described in a percutaneously treated patient[ 43 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Local ablation of pancreatic tumors: State of the art and future perspectives

Granata

Grassi

Fusco

et al. 2021

WJG

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BACKGROUND Currently, the technologies most commonly used to treat locally advanced pancreatic cancer are radiofrequency ablation (RFA), microwave ablation, and irreversible (IRE) or reversible electroporation combined with low doses of chemotherapeutic drugs. AIM To report an overview and updates on ablative techniques in pancreatic cancer. METHODS Several electronic databases were searched. The search covered the years from January 2000 to January 2021. Moreover, the reference lists of the found papers were analysed for papers not indexed in the electronic databases. All titles and abstracts were analysed. RESULTS We found 30 studies (14 studies for RFA, 3 for microwave therapy, 10 for IRE, and 3 for electrochemotherapy), comprising 1047 patients, which were analysed further. Two randomized trials were found for IRE. Percutaneous and laparotomy approaches were performed. In the assessed patients, the median maximal diameter of the lesions was in the range of 2.8 to 4.5 cm. All series included patients unfit for surgical treatment, but Martin et al assessed a subgroup of patients with borderline resectable tumours who underwent resection with margin attenuation with IRE. Most studies administered chemotherapy prior to ablative therapies. However, several studies suggest that the key determinant of improved survival is attributable to ablative treatment alone. Nevertheless, the authors suggested chemotherapy before local therapies for several reasons. This strategy may not only downstage a subgroup of patients to curative-intent surgery but also support to recognize patients with biologically unfavourable tumours who would likely not benefit from ablation treatments. Ablation therapies seem safe based on the 1047 patients assessed in this review. The mortality rate ranged from 1.8% to 2%. However, despite the low mortality, the reported rates of severe post procedural complications ranged from 0%-42%. Most reported complications have been self-limiting and manageable. Median overall survival varied between 6.0 and 33 mo. Regarding the technical success rate, assessed papers reported an estimated rate in the range of 85% to 100%. However, the authors reported early recurrence after treatment. A distinct consideration should be made on whether local treatments induce an immune response in the ablated area. Preclinical and clinical studies have shown that RFA is a promising mechanism for inducing antigen-presenting cell infiltration and enhancing the systemic antitumour T-cell immune response and tumour regression. CONCLUSION In the management of patients with pancreatic cancer, the possibility of a multimodal approach should be considered, and conceptually, the combination of RFA with immunotherapy represents a novel angle of attack against this tumour.

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Section: Discussionmentioning

confidence: 99%

Local ablation of pancreatic tumors: State of the art and future perspectives

Granata

Grassi

Fusco

et al. 2021

WJG

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“…HT promotes antigen presenting cell (APC) activation and antigen-specific naïve CD8+ T cell differentiation, allows CD4+ T cells to shift towards the Th1 phenotype, and transforms regulatory T cells (Tregs) into Th17 cells[ 32 ]. In a mouse model of PDAC, RFA induced an increase in infiltrating CD8+ T cells and a decrease in Treg cells but showed no difference in the proportion of infiltrating CD4+ lymphocytes[ 33 ]. HT has been shown to induce chemokine production, such as CCL21, combined with adhesion factors (selectin, integrin, ICAM-1), thus allowing an increase in the interactions between lymphocytes and endothelial cells and the homing of lymphocytes[ 34 - 37 ].…”

Section: Htmentioning

confidence: 99%

“…Membrane HSP has been found to be a tumor-specific target for natural killer cells, whereas extracellular HSP can be considered a potent adjuvant to facilitate tumor antigen presentation and the induction of antitumor immunity[ 32 , 41 , 42 ]. More specifically, HSP70 has been shown to induce tumor cell proliferation in a mouse model of PDAC by activating AKT-mTOR signaling[ 33 ]. HSP60 has been shown to induce IFNg secretion and T cell upregulation[ 43 ].…”

Section: Htmentioning

confidence: 99%

Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma

Lambin¹,

Lafon²,

Drainville³

et al. 2022

WJG

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Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment (TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients’ quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy - most commonly using a local high single dose - are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.

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“…HSP-70, mainly exposed in the peripheral non-coagulative ablation zone, is elevated in the serum of patients after RFA, which can lead to an immunological anticancer response through activation and maturation of DCs [50,51]. However, in this peripheral zone, created by diffusion of heat outwards, IL-6, HSP-70, and hypoxia-related pathways have also been implicated to stimulate outgrowth of tumor cells in this area, thus potentially causing (early) recurrences [52][53][54][55].…”

Section: Immunomodulation After Rfamentioning

confidence: 99%

Locally Advanced Pancreatic Cancer: Percutaneous Management Using Ablation, Brachytherapy, Intra-arterial Chemotherapy, and Intra-tumoral Immunotherapy

et al. 2021

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Purpose of Review Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasms, bearing a terrible prognosis. Stage III tumors, also known as locally advanced pancreatic cancer (LAPC), are unresectable, and current palliative chemotherapy regimens have only modestly improved survival in these patients. At this stage of disease, interventional techniques may be of value and further prolong life. The aim of this review was to explore current literature on locoregional percutaneous management for LAPC. Recent Findings Locoregional percutaneous interventional techniques such as ablation, brachytherapy, and intra-arterial chemotherapy possess cytoreductive abilities and have the potential to increase survival. In addition, recent research demonstrates the immunomodulatory capacities of these treatments. This immune response may be leveraged by combining the interventional techniques with intra-tumoral immunotherapy, possibly creating a durable anti-tumor effect. This multimodality treatment approach is currently being examined in several ongoing clinical trials. Summary The use of certain interventional techniques appears to improve survival in LAPC patients and may work synergistically when combined with immunotherapy. However, definitive conclusions can only be made when large prospective (randomized controlled) trials confirm these results.

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Radiofrequency ablation in combination with an mTOR inhibitor restrains pancreatic cancer growth induced by intrinsic HSP70

Cited by 11 publications

References 49 publications

Local ablation of pancreatic tumors: State of the art and future perspectives

Local ablation of pancreatic tumors: State of the art and future perspectives

Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma

Locally Advanced Pancreatic Cancer: Percutaneous Management Using Ablation, Brachytherapy, Intra-arterial Chemotherapy, and Intra-tumoral Immunotherapy

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