An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome |
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| Authors: | Peter Hollander Klaus Rostgaard Karin E. Smedby Daniel Molin Angelica Loskog Peter de Nully Brown Gunilla Enblad Rose‐Marie Amini Henrik Hjalgrim Ingrid Glimelius |
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| Affiliation: | 1. Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;2. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark;3. Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden;4. Hematology Center, Karolinska University Hospital, Stockholm, Sweden;5. Clinical immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;6. Department of Haematology, Rigshospitalet, Copenhagen, Denmark;7. Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden |
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| 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. |
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| Keywords: | Hodgkin lymphoma Regulatory T lymphocytes Tumor microenvironment |
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