1. Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma.
- Author
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Garcia-Marquez MA, Thelen M, Reinke S, Keller D, Wennhold K, Lehmann J, Veldman J, Borchmann S, Rosenwald A, Sasse S, Diepstra A, Borchmann P, Engert A, Klapper W, von Bergwelt-Baildon M, Bröckelmann PJ, and Schlößer HA
- Subjects
- Antigens, Neoplasm immunology, Female, Hodgkin Disease immunology, Humans, Immunity drug effects, Male, T-Lymphocytes immunology, Hodgkin Disease drug therapy, Immune Checkpoint Inhibitors therapeutic use, Nivolumab therapeutic use, T-Lymphocytes drug effects
- 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., (© 2021. The Author(s).)
- Published
- 2022
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