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

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.

• Authors: Maria A Garcia-Marquez, Martin Thelen, Sarah Reinke, Diandra Keller, Kerstin Wennhold, Jonas Lehmann, Johanna Veldman, Sven Borchmann, Andreas Rosenwald, Stephanie Sasse, Arjan Diepstra, Peter Borchmann, Andreas Engert, Wolfram Klapper, Michael von Bergwelt-Baildon, Paul J Bröckelmann, Hans A Schlößer
• Journal: Leukemia (Leukemia) Vol. 36 Issue 3 Pg. 760-771 (03 2022) ISSN: 1476-5551 [Electronic] England
• PMID: 34584203 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Antigens, Neoplasm
• Immune Checkpoint Inhibitors
• Nivolumab

Topics

• Antigens, Neoplasm (immunology)
• Female
• Hodgkin Disease (drug therapy, immunology)
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Immunity (drug effects)
• Male
• Nivolumab (therapeutic use)
• T-Lymphocytes (drug effects, immunology)