Leuchte, Katharina, Staib, Elena, Thelen, Martin ORCID: 0000-0002-2785-9726, Goedel, Philipp, Lechner, Axel, Zentis, Peter, Garcia-Marquez, Maria, Waldschmidt, Dirk, Datta, Rabi Raj, Wahba, Roger, Wybranski, Christian, Zander, Thomas, Quaas, Alexander, Drebber, Uta, Stippel, Dirk Ludger, Bruns, Christiane, Von Bergwelt-Baildon, Michael, Wennhold, Kerstin and Schloesser, Hans Anton . Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma. Cancer Immunol. Immunother.. NEW YORK: SPRINGER. ISSN 1432-0851

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Leuchte, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Staib, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thelen, MartinUNSPECIFIEDorcid.org/0000-0002-2785-9726UNSPECIFIED
Goedel, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lechner, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zentis, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Marquez, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waldschmidt, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Datta, Rabi RajUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wahba, RogerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wybranski, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quaas, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drebber, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stippel, Dirk LudgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Von Bergwelt-Baildon, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wennhold, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schloesser, Hans AntonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-315877
DOI: 10.1007/s00262-020-02734-1
Journal or Publication Title: Cancer Immunol. Immunother.
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-0851
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
T-CELL SUBSETS; RADIOFREQUENCY ABLATION; THERMAL ABLATION; CTLA-4 BLOCKADE; EXPRESSION; CANCERMultiple languages
Oncology; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31587

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