Epstein Barr Virus Recruits PDL1 Positive Cells at the Microenvironment in Pediatric Hodgkin Lymphoma

Abstract

Classic Hodgkin lymphoma (cHL) is a lymphoid neoplasm in which the immune microenvironment contributes to the lymphomagenesis process. Epstein Barr virus (EBV) presence also influences cHL microenvironment composition and contributes to pathogenesis. Our aim was to evaluate the PD1 / PDL1 pathway and EBV influence on this pathway in pediatric cHL. Methods: 80 pediatric patients were analyzed. EBV presence was assessed by in situ hybridization (HIS), the expression of PDL1 in the microenvironment (PDL1mic) and PDL1 in the HRS tumor cells (PDL1HRS) and PD1 in the microenvironment (PD1mic) by immunohistochemistry (IHC) expressing the results as +cells/ mm2. PDL1 genetic alterations were analyzed in a subgroup of 37 pediatric patients by FISH, following the criteria of: genetic gain (PDL1 / CEP9 <3: 1), amplification (PDL1 / CEP9 ≥3: 1) or diplody (PDL1 / CEP9=1:1). The survival was evaluated in relation to the expression of PDL1 mic, PDL1 HRS and PD1 mic. Results: No significant differences were observed in the PD1mic count or in the PDL1 HRS count between the EBV + and EBV- cases (P> 0.05; Mann Whitney test). Unexpectedly, only 38% of pediatric cHL showed PDL1 genetic alterations by FISH (8% amplification, 16% gain and 13% gain + amplification) and no differences were observed in EBV + vs EBV- cases (p> 0.05, exact test of Fisher). In the cHL EBV + cases, a significant increase in PDL1mic + cells was detected in the microenvironment (p> 0.05, Mann Whitney test). Neither PD1mic nor PDL1 expression in HRS cells or in the microenvironment was associated with survival in pediatric patients (p> 0.05, log-rank test) .Conclusions: Although our group previously described an environment of high cytotoxicity in pediatric EBV + cHL, it could be counteracted by a PDL1 + cell niche in the microenvironment, leading to unsuccessful elimination of EBV+ HRS tumor cells.