Peter Hollander1, Klaus Rostgaard2, Karin E Smedby3,4, Daniel Molin1, Angelica Loskog5, Peter de Nully Brown6, Gunilla Enblad1, Rose-Marie Amini7, Henrik Hjalgrim2,6, Ingrid Glimelius1,3. 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.
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.
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.
Authors: Alex Reza Gholiha; Peter Hollander; Ingrid Glimelius; Gustaf Hedstrom; Daniel Molin; Henrik Hjalgrim; Karin E Smedby; Jamileh Hashemi; Rose-Marie Amini; Gunilla Enblad Journal: Blood Adv Date: 2021-03-23
Authors: Philippa Li; Ji Yuan; Fahad Shabbir Ahmed; Austin McHenry; Kai Fu; Guohua Yu; Hongxia Cheng; Mina L Xu; David L Rimm; Zenggang Pan Journal: Front Oncol Date: 2021-08-30 Impact factor: 6.244
Authors: Alex Reza Gholiha; Peter Hollander; Liza Löf; Ingrid Glimelius; Gustaf Hedstrom; Daniel Molin; Henrik Hjalgrim; Karin E Smedby; Jamileh Hashemi; Rose-Marie Amini; Gunilla Enblad Journal: Br J Haematol Date: 2022-03-17 Impact factor: 8.615