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

TY - JOUR

T1 - An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome

AU - Hollander, Peter

AU - Rostgaard, Klaus

AU - Smedby, Karin E.

AU - Molin, Daniel

AU - Loskog, Angelica

AU - de Nully Brown, Peter

AU - Enblad, Gunilla

AU - Amini, Rose Marie

AU - Hjalgrim, Henrik

AU - Glimelius, Ingrid

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Hodgkin lymphoma

KW - Regulatory T lymphocytes

KW - Tumor microenvironment

U2 - 10.1111/ejh.12987

DO - 10.1111/ejh.12987

M3 - Journal article

C2 - 29064587

AN - SCOPUS:85033724025

SN - 0902-4441

VL - 100

SP - 88

EP - 97

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 1

ER -