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- Title
An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome.
- Authors
Hollander, Peter; Rostgaard, Klaus; Smedby, Karin E.; Molin, Daniel; Loskog, Angelica; de Nully Brown, Peter; Enblad, Gunilla; Amini, Rose‐Marie; Hjalgrim, Henrik; Glimelius, Ingrid
- Abstract
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.
- Subjects
HODGKIN'S disease; T cells; EOSINOPHILS; MAST cells; EPSTEIN-Barr virus; IMMUNOTHERAPY
- Publication
European Journal of Haematology, 2018, Vol 100, Issue 1, p88
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1111/ejh.12987