Abstract
Tumor-infiltrating macrophages are associated with adverse outcome in adult classical Hodgkin lymphoma (cHL). We have previously shown age-related changes in the lymphocyte composition of pediatric cHL. We therefore hypothesized that the number, function, and prognostic impact of macrophages in pediatric cHL would be different from adult cases. We analyzed the number of macrophages and dendritic cells (DC) in the tumor microenvironment of pediatric cHL by immunohistochemistry. Results were analyzed in context of age, histologic characteristics, Epstein-Barr virus (EBV) status, clinical follow-up, and our previous study of T-cell populations in these cases. One hundred cHL cases were studied, including 69% nodular sclerosis and 23% mixed cellularity cases. A total of 44.8% of cases were EBV-positive. Patients ≤10 years displayed more CD14(+) cells (P = 0.025). In comparison with nodular sclerosis, mixed cellularity was characterized by higher numbers of CD14(+), (P = 0.003) and CD163(+) cells (P = 0.027). EBV(+) cases exhibited higher numbers of CD14(+) (P < 0.0005), CD68(+) (P = 0.005), and CD163(+) cells (P = 0.02). CD68-positive cells did not display an effect on outcome. Worse overall survival was observed in cases with CD163/CD8 ratio ≥2 (P = 0.007). High numbers of CD163(+) cells were associated with worse progression-free survival (PFS; P = 0.015). Furthermore, high numbers of CD163(+) and granzyme B(+) cells were associated with worse PFS in EBV-negative (P = 0.005) but not in EBV-positive cases. Our results suggest that macrophage composition in pediatric cHL is distinct from adults. Functional status of macrophages and their value as prognostic indicators in pediatric cHL may depend on EBV status.
Highlights
Classical Hodgkin lymphoma microenvironment is modulated by cytokines and chemokines produced by Hodgkin/Reed–Sternberg (HRS) cells and is thought to contribute to tumor cell growth and escape from immunosurveillance [1]
Our results suggest that macrophage composition in pediatric Classical Hodgkin lymphoma (cHL) is distinct from adults
Functional status of macrophages and their value as prognostic indicators in pediatric cHL may depend on EpsteinBarr virus (EBV) status
Summary
Classical Hodgkin lymphoma (cHL) microenvironment is modulated by cytokines and chemokines produced by Hodgkin/Reed–Sternberg (HRS) cells and is thought to contribute to tumor cell growth and escape from immunosurveillance [1]. We have shown recently that in EpsteinBarr virus (EBV)þ pediatric cHL the tumor microenvironment is characterized by a cytotoxic/T-helper cell 1 (TH1) profile [2]. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/). Less than 1 in the tumor microenvironment were associated with an improved outcome. We hypothesized that in pediatric EBVþ cHL an effective cytotoxic immune response directed against viral or tumor antigens may be triggered in the tumor microenvironment [2,3]. Recent studies have consistently reported that high numbers of tumor-associated macrophages (TAM) are associated with adverse outcome in adult cHL [4,5,6]. The specific role of TAM in pediatric cHL has not been studied
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