Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma
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ORIGINAL ARTICLE
Microwave ablation enhances tumor‑specific immune response in patients with hepatocellular carcinoma Katharina Leuchte1,2 · Elena Staib1 · Martin Thelen1 · Philipp Gödel1,2 · Axel Lechner3 · Peter Zentis4 · Maria Garcia‑Marquez1 · Dirk Waldschmidt5 · Rabi Raj Datta1,6 · Roger Wahba6 · Christian Wybranski7 · Thomas Zander2 · Alexander Quaas8 · Uta Drebber8 · Dirk Ludger Stippel6 · Christiane Bruns6 · Michael von Bergwelt‑Baildon9,10 · Kerstin Wennhold1 · Hans Anton Schlößer1,6 Received: 1 April 2020 / Accepted: 20 September 2020 © The Author(s) 2020
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. Keywords Immunogenic cell death · Immunotherapy · Antigens · Abscopal effect Katharina Leuchte and Elena Staib contributed equally and thus share first authorship. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02734-1) contains supplementary material, which is available to authorized users.
Abbreviations CT Center of the tumor DFS Disease-free survival DNAM DNAX Accessory Molecule-1 4
* Katharina Leuchte katharina.leuchte@uk‑koeln.de
Cluster of Excellence in Aging‑Associated Disease, Core Facility Imaging, University of Cologne, Köln, Germany
5
Department of Gastroenterology and Hepatology, Univer
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