Universität zu Köln

Garcia-Marquez, Maria A., Thelen, Martin ORCID: 0000-0002-2785-9726, Reinke, Sarah, Keller, Diandra, Wennhold, Kerstin, Lehmann, Jonas, Veldman, Johanna ORCID: 0000-0003-4253-0870, Borchmann, Sven ORCID: 0000-0001-6662-6864, Rosenwald, Andreas, Sasse, Stephanie, Diepstra, Arjan ORCID: 0000-0001-9239-1050, Borchmann, Peter, Engert, Andreas, Klapper, Wolfram, Von Bergwelt-Baildon, Michael, Broeckelmann, Paul J. and Schloesser, Hans A. (2022). Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma. Leukemia, 36 (3). S. 760 - 772. LONDON: SPRINGERNATURE. ISSN 1476-5551

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Garcia-Marquez, Maria A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thelen, Martin UNSPECIFIED orcid.org/0000-0002-2785-9726 UNSPECIFIED Reinke, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Keller, Diandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Wennhold, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Jonas UNSPECIFIED UNSPECIFIED UNSPECIFIED Veldman, Johanna UNSPECIFIED orcid.org/0000-0003-4253-0870 UNSPECIFIED Borchmann, Sven UNSPECIFIED orcid.org/0000-0001-6662-6864 UNSPECIFIED Rosenwald, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Sasse, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Diepstra, Arjan UNSPECIFIED orcid.org/0000-0001-9239-1050 UNSPECIFIED Borchmann, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Engert, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Klapper, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Von Bergwelt-Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Broeckelmann, Paul J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloesser, Hans A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-596859
DOI:	10.1038/s41375-021-01421-z
Journal or Publication Title:	Leukemia
Volume:	36
Number:	3
Page Range:	S. 760 - 772
Date:	2022
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1476-5551
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language T-CELLS; PHASE-II; EXPRESSION; ANTIGENS; MICROENVIRONMENT; PEMBROLIZUMAB; MECHANISMS; RECEPTORS; NIVOLUMAB; BLOCKADE Multiple languages Oncology; Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59685