Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma.

Autor: Garcia-Marquez MA; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. maria.garcia-marquez@uk-koeln.de., Thelen M; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Reinke S; Institute of Pathology, University of Kiel, Kiel, Germany., Keller D; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Wennhold K; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Lehmann J; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Veldman J; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Borchmann S; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), German Hodgkin Study Group (GHSG), University of Cologne, Cologne, Germany., Rosenwald A; Department of Pathology, University of Würzburg, Würzburg, Germany., Sasse S; Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), German Hodgkin Study Group (GHSG), University of Cologne, Cologne, Germany., Diepstra A; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Borchmann P; Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), German Hodgkin Study Group (GHSG), University of Cologne, Cologne, Germany., Engert A; Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), German Hodgkin Study Group (GHSG), University of Cologne, Cologne, Germany., Klapper W; Institute of Pathology, University of Kiel, Kiel, Germany., von Bergwelt-Baildon M; Department of Internal Medicine III, University Hospital, Ludwig Maximilians University, Munich, Germany., Bröckelmann PJ; Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), German Hodgkin Study Group (GHSG), University of Cologne, Cologne, Germany. paul.broeckelmann@uk-koeln.de.; Mildred Scheel School of Oncology Aachen Bonn Cologne Düsseldorf (MSSO ABCD), Faculty of Medicine and University of Cologne, Cologne, Germany. paul.broeckelmann@uk-koeln.de.; Max Planck Institute for Biology of Ageing, Cologne, Germany. paul.broeckelmann@uk-koeln.de., Schlößer HA; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital Cologne, Department of General, Visceral, Cancer and Transplantation Surgery, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD) and University of Cologne, Cologne, Germany.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2022 Mar; Vol. 36 (3), pp. 760-771. Date of Electronic Publication: 2021 Sep 28.
DOI: 10.1038/s41375-021-01421-z
Abstrakt: While classical Hodgkin lymphoma (HL) is highly susceptible to anti-programmed death protein 1 (PD1) antibodies, the exact modes of action remain controversial. To elucidate the circulating lymphocyte phenotype and systemic effects during anti-PD1 1st-line HL treatment we applied multicolor flow cytometry, FluoroSpot and NanoString to sequential samples of 81 HL patients from the NIVAHL trial (NCT03004833) compared to healthy controls. HL patients showed a decreased CD4 T-cell fraction, a higher percentage of effector-memory T cells and higher expression of activation markers at baseline. Strikingly, and in contrast to solid cancers, expression for 10 out of 16 analyzed co-inhibitory molecules on T cells (e.g., PD1, LAG3, Tim3) was higher in HL. Overall, we observed a sustained decrease of the exhausted T-cell phenotype during anti-PD1 treatment. FluoroSpot of 42.3% of patients revealed T-cell responses against ≥1 of five analyzed tumor-associated antigens. Importantly, these responses were more frequently observed in samples from patients with early excellent response to anti-PD1 therapy. In summary, an initially exhausted lymphocyte phenotype rapidly reverted during anti-PD1 1st-line treatment. The frequently observed IFN-y responses against shared tumor-associated antigens indicate T-cell-mediated cytotoxicity and could represent an important resource for immune monitoring and cellular therapy of HL.
(© 2021. The Author(s).)
Databáze: MEDLINE
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