An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome

Research output: Contribution to journalJournal articlepeer-review

  • Peter Hollander
  • Klaus Rostgaard
  • Karin E. Smedby
  • Daniel Molin
  • Angelica Loskog
  • Brown, Peter de Nully
  • Gunilla Enblad
  • Rose Marie Amini
  • Henrik Hjalgrim
  • Ingrid Glimelius

Objective: The classical Hodgkin lymphoma (cHL) tumor microenvironment shows an ongoing inflammatory response consisting of varying degrees of infiltrating eosinophils, mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome. Methods: Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression. Results: The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9-year follow-up) in age-adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05-3-15). Epstein-Barr virus (EBV)-positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis. Conclusions: Abundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.

Original languageEnglish
JournalEuropean Journal of Haematology
Issue number1
Pages (from-to)88-97
Number of pages10
Publication statusPublished - 2018

    Research areas

  • Hodgkin lymphoma, Regulatory T lymphocytes, Tumor microenvironment

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