Classic Hodgkin lymphoma in Guatemalan children of age less than six years: analysis of immune regulatory pathways and the tumor microenvironment

Abstract

Classic Hodgkin lymphoma (cHL) in young children (ages 0–6) is rare in high income countries (HICs) but is more prevalent in low- and middle-income countries (LMICs) like Guatemala. Given that the majority of cHL studies have evaluated adolescent/adults, and the immune system changes with age, we sought to characterize Epstein-Barr virus (EBV) expression, immune regulatory pathway markers and the tumor microenvironment in 42 children ages 0–6 with cHL from Guatemala. We found a very high frequency of EBV expression (97.5%). Hodgkin cells showed increased expression of PD1 ligands and CD137, indicative of shared immune regulatory mechanisms with adult cHL. Pediatric cHL also showed an increase in CD8+ tumor infiltrating lymphocytes and tumor associated macrophages within the tumor microenvironment. Despite 25 having high risk disease, only 4 patients died from progressive disease, relapse or infection.