PD1+ Cells in Pediatric Classical Hodgkin Lymphoma is Associated with Better Outcome

Abstract

Classical Hodgkin lymphoma (cHL) is characterized by few neoplastic cells in a background of inflammatory cells. Many studies have described the T cell composition of tumour microenvironment in adult cases and we have demonstrated differences between pediatric and adult cHL in this respect. Two studies recently described that high numbers of PD1+ cells were associated with worse survival in adult cHL. PD1 is a receptor expressed by CD8+ and CD4+ T cells upon activation, as well as by T follicular helper cells, exhausted CD8+ T cells and effector memory CD8+ T cells. The objective of this study was to evaluate PD1+ cells in 100 paediatric cHL cases (3 to 18 y, median: 14 y) using immunohistochemistry and computer assisted microscopical analysis. The results were compared with the other T-cell populations as determined in our previous study of these cases. A median of 5 PD1+ cells/mm2 was observed (1 to 363 cells/mm2), while 40% of cases did not show any PD1+ cell. A direct correlation was observed between the numbers of PD1+ and CD4+ cells (P = 0.018), as well as PD1+ and CD8+ cells (P = 0.02). Higher numbers of PD1+ cells were observed in cases with cytotoxic microenvironment profile (P = 0.016), as disclosed by the ratio TIA1+ cells/FOXP3+ cells > 1.5. The numbers of PD1+ cells were not associated with age group or EBV-status. Cases with higher numbers of PD1+ cells (> 5 cells/mm2) were associated with better 5-years overall survival (P = 0.019). Our results suggest that the majority of PD1+ cells in the tumour microenvironment of paediatric cHL may contribute to the immune response against the neoplastic cells. A more detailed characterization of these cells is in progress.