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

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. and Bröckelmann, P.J. and Iaccarino, I. and Garcia-Marquez, M. and Borchmann, S. and Jochims, F. and Kotrova, M. and Pal, K. and Brüggemann, M. and Hartmann, E. and Sasse, S. and Kobe, C. and Mathas, S. and Soekler, M. and Keller, U. and Bormann, M. and Zimmermann, A. and Richter, J. and Fuchs, M. and von Tresckow, B. and Borchmann, P. and Schlößer, H. and von Bergwelt-Baildon, M. and Rosenwald, A. and 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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