Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1

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Item Type:	Article
Title:	Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1
Creators Name:	Reinke, S., Bröckelmann, P.J., Iaccarino, I., Garcia-Marquez, M., Borchmann, S., Jochims, F., Kotrova, M., Pal, K., Brüggemann, M., Hartmann, E., Sasse, S., Kobe, C., Mathas, S., Soekler, M., Keller, U., Bormann, M., Zimmermann, A., Richter, J., Fuchs, M., von Tresckow, B., Borchmann, P., Schlößer, H., von Bergwelt-Baildon, M., Rosenwald, A., Engert, A. and Klapper, W.
Abstract:	Classic Hodgkin lymphoma (cHL) is the cancer type most susceptible to anti-programmed-death-receptor-1 (PD1) treatment and characterized by scarce Hodgkin and Reed-Sternberg cells (HRSC) perpetuating a unique tumor microenvironment (TME). Whilst in solid tumors anti-PD1 effects appear largely mediated by cytotoxic CD8+ T-cells, HRSC frequently lack major histocompatibility complex expression and the mechanism of anti-PD1 efficacy in cHL is unclear. Rapid clinical response and high interim complete response rate to anti-PD1 based 1st-line treatment was recently reported for patients with early-stage unfavorable cHL treated in the GHSG phase II NIVAHL trial. To investigate the mechanisms underlying this very early response to anti-PD1 treatment, we analyzed paired biopsies and blood samples obtained in NIVAHL patients before and during the first days of nivolumab 1st-line cHL therapy. Mirroring the rapid clinical response, HRSC had disappeared from the tissue within days after the first nivolumab application. The TME shows a reduction of Tr1 T-cells and PD-L1+ tumor associated macrophages (TAM) already at this early timepoint of treatment. Interestingly, neither a cytotoxic immune-response nor a clonal T-cell expansion was observed in the tumors or peripheral blood. These early changes of the TMA were distinct from alterations found in a separate set of cHL biopsies at relapse during anti-PD1 therapy. We identify a unique very early histologic response pattern to anti-PD1 therapy in cHL suggestive for withdrawal of pro-survival factors rather than induction of an adaptive anti-tumor immune response as main mechanism of action.
Keywords:	Cytotoxic T-Lymphocytes, Hodgkin Disease, Immunological Antineoplastic Agents, Lymphocyte Activation, Nivolumab, Programmed Cell Death 1 Receptor, Tumor Microenvironment, Tumor-Associated Macrophages
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	136
Number:	25
Page Range:	2851-2863
Date:	17 December 2020
Official Publication:	https://doi.org/10.1182/blood.2020008553
PubMed:	View item in PubMed

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