APA
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Garcia-Marquez, M., Thelen, M., Reinke, S., Keller, D., Wennhold, K., Lehmann, J., … Schlößer, H. (2021). Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma. Leukemia.
Chicago/Turabian
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Garcia-Marquez, M., M. Thelen, S. Reinke, D. Keller, K. Wennhold, J. Lehmann, J. Veldman, et al. “Reverted Exhaustion Phenotype of Circulating Lymphocytes as Immune Correlate of Anti-PD1 First-Line Treatment in Hodgkin Lymphoma.” Leukemia (2021).
MLA
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Garcia-Marquez, M., et al. “Reverted Exhaustion Phenotype of Circulating Lymphocytes as Immune Correlate of Anti-PD1 First-Line Treatment in Hodgkin Lymphoma.” Leukemia, 2021.
BibTeX Click to copy
@article{m2021a,
title = {Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma},
year = {2021},
journal = {Leukemia},
author = {Garcia-Marquez, M. and Thelen, M. and Reinke, S. and Keller, D. and Wennhold, K. and Lehmann, J. and Veldman, J. and Borchmann, S. and Rosenwald, A. and Sasse, S. and Diepstra, A. and Borchmann, P. and Engert, A. and Klapper, W. and von Bergwelt-Baildon, M. V. and Bröckelmann, P. and Schlößer, H.}
}
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.