Reinke, Sarah, Broeckelmann, Paul J., Iaccarino, Ingram, Garcia-Marquez, Maria, Borchmann, Sven, Jochims, Franziska, Kotrova, Michaela ORCID: 0000-0001-5394-1072, Pal, Karol, Brueggemann, Monika, Hartmann, Elena, Sasse, Stephanie, Kobe, Carsten, Mathas, Stephan, Soekler, Martin, Keller, Ulrich, Bormann, Matthias, Zimmermann, Andreas, Richter, Julia, Fuchs, Michael, von Tresckow, Bastian, Borchmann, Peter, Schloesser, Hans, von Bergwelt-Baildon, Michael, Rosenwald, Andreas, Engert, Andreas and Klapper, Wolfram (2020). Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1. Blood, 136 (25). S. 2851 - 2864. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

Classic Hodgkin lymphoma (cHL) is the cancer type most susceptible to antibodies targeting programmed cell death protein 1 (PD1) and is characterized by scarce Hodgkin and Reed-Sternberg cells (HRSCs), perpetuating a unique tumor microenvironment (TME). Although anti-PD1 effects appear to be largely mediated by cytotoxic CD8(+) T cells in solid tumors, HRSCs frequently lack major histocompatibility complex expression, and the mechanism of anti-PD1 efficacy in cHL is unclear. Rapid clinical responses and high interim complete response rates to anti-PD1 based first-line treatment were recently reported for patients with early-stage unfavorable cHL treated in the German Hodgkin Study Group phase 2 NIVAHL trial. To investigate the mechanisms underlying this very early response to anti-PD1 treatment, we analyzed paired biopsies and blood samples obtained from NIVAHL patients before and during the first days of nivolumab first-line cHL therapy. Mirroring the rapid clinical response, HRSCs had disappeared from the tissue within days after the first nivolumab application. The TME already shows a reduction in type 1 regulatory T cells and PD-L1(+) tumor-associated macrophages at this early time point of treatment. Interestingly, a cytotoxic immune response and a clonal T-cell expansion were not observed in the tumors or peripheral blood. These early changes in the TME were distinct from alterations found in a separate set of cHL biopsies at relapse during anti-PD1 therapy. We identify a unique very early histologic response pattern to anti-PD1 therapy in cHL that is suggestive of withdrawal of prosurvival factors, rather than induction of an adaptive antitumor immune response, as the main mechanism of action.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Reinke, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Broeckelmann, Paul J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iaccarino, IngramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Marquez, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borchmann, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jochims, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kotrova, MichaelaUNSPECIFIEDorcid.org/0000-0001-5394-1072UNSPECIFIED
Pal, KarolUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brueggemann, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sasse, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kobe, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mathas, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soekler, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keller, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bormann, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmermann, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richter, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuchs, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Tresckow, BastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borchmann, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schloesser, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Bergwelt-Baildon, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenwald, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engert, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klapper, WolframUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-307810
DOI: 10.1182/blood.2020008553
Journal or Publication Title: Blood
Volume: 136
Number: 25
Page Range: S. 2851 - 2864
Date: 2020
Publisher: AMER SOC HEMATOLOGY
Place of Publication: WASHINGTON
ISSN: 1528-0020
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ANALYSIS REVEALS; PD-1 BLOCKADE; TRANSPLANTATION; EXPRESSION; NIVOLUMAB; MULTICOHORT; THERAPY; FAILUREMultiple languages
HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/30781

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