M1 macrophage polarization prevails in pediatric Hodgkin Lymphoma from Argentina regardless of Epstein Barr virus presence

MAGALHÃES BARROS, M; GARCIA LOMBARDI, M; PAOLA ANDREA CHABAY; JIMENEZ O; DE MATTEO E; NIEDOBITEK G; COHEN, M; PRECIADO MV

Colonia

Congreso; The 11th International Symposium on Hodgkin Lymphoma; 2018

German Hodgkin Study Group

Background: The microenvironment in cHL is a complex network of different cell types, which enable cancer pathogenesis and progression. Even though microenvironment composition in adult cHL has been largely studied, only a few studies were performed in pediatric cHL, in which age and EBV infection may have a key role. In addition, EBV association with cHL in Argentina is significant in patients under 10 years old. Therefore, our aim was to characterize microenviroment composition in a pediatric cHL series. Methods: Formalin-fixed paraffin-embedded (FFPE) biopsy samples from 46 patients were collected, from the archives at Pathology Division, Ricardo Gutierrez Children?s Hospital in Buenos Aires, Argentina. Tissue Microarray (TMA) blocks including 46 cHL cases were constructed. Tumor microenvironment immunophenotyping was performed with a panel of antibodies: CD4, CD8, Foxp3 (Treg), granzyme B (GrB). Macrophage polarization was assessed by doble staining with pSTAT1 or CMAF followed by CD68 or CD163. Co-expression of pSTAT1 with CD68 or CD163 identified M1-polarized macrophages, while co-expression of CMAF with CD68 or CD163, identified M2-polarized macrophages. Results: By means of CD68, 81% of cases displayed M1 polarization (CD68+pSTAT1+ / CD68+CMaf+ >1.5), 13% exhibited M2 pattern (CD163+pSTAT1+ / CD163+CMaf+ 1.5), 37% proved to be M2 polarized (CD163+pSTAT1+ / CD163+CMAF+ 0.05, Mann Whiney test), whereas GrB+ cell numbers were significantly higher under M1 polarized condition (p=0.0178, Mann Whitney test). Survival was influenced neither by macrophage presence nor by cytotoxic or immunoregulatory-rich status. Conclusions: This study reveals that age has an impact on microenviroment composition in cHL, given the fact that M2 polarized status previously described in adult cHL may not be prevalent in children younger than 10 years. The cytotoxic and antitumor M1 environment in young pediatric patient might be ineffective to control lymphomagenesis process.