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Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma.

ABSTRACT: Thermal ablative therapies are standard treatments for localized hepatocellular carcinoma (HCC). In addition to local tumor destruction, ablation leads to abscopal effects in distant lesions most likely mediated by an anti-tumor immune response. Although microwave ablation (MWA) is increasingly substituting other ablative techniques, its systemic immunostimulatory effects are poorly studied. We analyzed tumor-specific immune responses in peripheral blood of HCC patients after thermal ablation with regard to T cell responses and disease outcome. While comprehensive flow cytometric analyses in sequential samples of a prospective patient cohort (n = 23) demonstrated only moderate effects of MWA on circulating immune cell subsets, fluorospot analyses of specific T cell responses against seven tumor-associated antigens (TTAs) revealed de-novo or enhanced tumor-specific immune responses in 30% of patients. This anti-tumor immune response was related to tumor control as Interferon-y and Interleukin-5 T cell responses against TAAs were more frequent in patients with a long-time remission (> 1 year) after MWA (7/16) compared to patients suffering from an early relapse (0/13 patients) and presence of tumor-specific T cell response (IFN-y and/or IL-5) was associated to longer progression-free survival (27.5 vs. 10.0 months). Digital image analysis of immunohistochemically stained archival HCC samples (n = 18) of patients receiving combined MWA and resection revealed a superior disease-free survival of patients with high T cell abundance at the time of thermal ablation (37.4 vs. 13.1 months). Our data demonstrates remarkable immune-related effects of MWA in HCC patients and provides additional evidence for a combination of local ablation and immunotherapy in this challenging disease.

SUBMITTER: Leuchte K

PROVIDER: S-EPMC7979675 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma.

Leuchte Katharina K Staib Elena E Thelen Martin M Gödel Philipp P Lechner Axel A Zentis Peter P Garcia-Marquez Maria M Waldschmidt Dirk D Datta Rabi Raj RR Wahba Roger R Wybranski Christian C Zander Thomas T Quaas Alexander A Drebber Uta U Stippel Dirk Ludger DL Bruns Christiane C von Bergwelt-Baildon Michael M Wennhold Kerstin K Schlößer Hans Anton HA

Cancer immunology, immunotherapy : CII 20201002 4

Thermal ablative therapies are standard treatments for localized hepatocellular carcinoma (HCC). In addition to local tumor destruction, ablation leads to abscopal effects in distant lesions most likely mediated by an anti-tumor immune response. Although microwave ablation (MWA) is increasingly substituting other ablative techniques, its systemic immunostimulatory effects are poorly studied. We analyzed tumor-specific immune responses in peripheral blood of HCC patients after thermal ablation wi ...[more]

PMID: 33006650

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Project description:Background and aimsImmune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). This study explored whether tumor response to ICIs in HCC varies among different organs.MethodsWe reviewed the data of patients with advanced HCC who had received ICIs. Patients with measurable diseases were enrolled. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used to evaluate the objective response to ICIs in tumors located in the liver, lung, lymph node, and other intra-abdominal sites.ResultsOf the 75 enrolled patients with advanced HCC, 51 and 11 patients had chronic hepatitis B virus and chronic hepatitis C virus infection, respectively. Regarding ICI treatment, 58, 1, and 16 patients had undergone anti-PD-1/anti-PD-L1 monoclonal antibody (mAb) alone, anti-CTLA4 mAb alone, and anti-PD-1 mAb plus anti-CTLA4 mAb, respectively; 20 and 55 patients had received ICIs as first-line or ≥second-line therapy. The overall objective response rate (ORR) was 28.0%. In total, 58, 34, 19, and 18 patients had measurable hepatic tumors and lung, lymph node, and other intra-abdominal metastases, and the corresponding organ-specific ORRs were 22.4, 41.2, 26.3, and 38.9%, respectively. Of the 39 patients who had both hepatic and extrahepatic tumors, 12 had disease control in extrahepatic tumors while progressive disease (PD) in hepatic tumors, whereas only 4 exhibited disease control in hepatic tumors while PD in extrahepatic tumors (p = 0.046, McNemar test). Of the 16 patients with only evaluable tumors in the liver and lungs at baseline, 8 had disease control in the lungs while PD in the liver, and none experienced disease control in the liver while PD in the lungs (p = 0.005).ConclusionsThe hepatic tumors of HCC may be less responsive to ICIs than extrahepatic lesions. Lung metastases responded most favorably to ICIs. The mechanisms underlying this differential response to ICIs warrant further investigation.

Project description:BackgroundHigh early recurrence (ER) of hepatocellular carcinoma (HCC) after microwave ablation (MWA) represents a sign of aggressive behavior and severely worsens prognosis. The aim of this study was to estimate the outcome of HCC following MWA and develop a response algorithmic strategy based on multiparametric MRI and clinical variables.MethodsIn this retrospective study, we reviewed the records of 339 patients (mean age, 62 ± 12 years; 106 men) treated with percutaneous MWA for HCC between January 2014 and December 2017 that were evaluated by multiparametric MRI. These patients were randomly split into a development and an internal validation group (3:1). Logistic regression analysis was used to screen imaging features. Multivariate Cox regression analysis was then performed to determine predictors of ER (within 2 years) of MWA. The response algorithmic strategy to predict ER was developed and validated using these data sets. ER rates were also evaluated by Kaplan-Meier analysis.ResultsBased on logistic regression analyses, we established an image response algorithm integrating ill-defined margins, lack of capsule enhancement, pre-ablative ADC, ΔADC, and EADC to calculate recurrence scores and define the risk of ER. In a multivariate Cox regression model, the independent risk factors of ER (p < 0.05) were minimal ablative margin (MAM) (HR 0.57; 95% CI 0.35 - 0.95; p < 0.001), the recurrence score (HR: 9.25; 95% CI 4.25 - 16.56; p = 0.021), and tumor size (HR 6.21; 95% CI 1.25 - 10.82; p = 0.014). Combining MAM and tumor size, the recurrence score calculated by the response algorithmic strategy provided predictive accuracy of 93.5%, with sensitivity of 92.3% and specificity of 83.1%. Kaplan-Meier estimates of the rates of ER in the low-risk and high-risk groups were 6.8% (95% CI 4.0 - 9.6) and 30.5% (95% CI 23.6 - 37.4), respectively.ConclusionA response algorithmic strategy based on multiparametric MRI and clinical variables was useful for predicting the ER of HCC after MWA.

Dataset Information

Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma.

Publications

Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma.

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