Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1
Autor/innen
- S. Reinke
- P.J. Bröckelmann
- I. Iaccarino
- M. Garcia-Marquez
- S. Borchmann
- F. Jochims
- M. Kotrova
- K. Pal
- M. Brüggemann
- E. Hartmann
- S. Sasse
- C. Kobe
- S. Mathas
- M. Soekler
- U. Keller
- M. Bormann
- A. Zimmermann
- J. Richter
- M. Fuchs
- B. von Tresckow
- P. Borchmann
- H. Schlößer
- M. von Bergwelt-Baildon
- A. Rosenwald
- A. Engert
- W. Klapper
Journal
- Blood
Quellenangabe
- Blood 136 (25): 2851-2863
Zusammenfassung
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.