Association of immune contexture, age, and tumor stage in peripheral neuroblastic tumors (PNT).

Abstract

e22006 Background: PNTs, a family of tumors arising in the embryonal remnants of the sympathetic nervous system, account for 7-10% of all tumors in children. NMYC status, stage, and age are the most important prognostic factors. The association of patient age and prognosis could be influenced by the maturity of immune system. The aims of this study were to describe the immune contexture in PNTs and to investigate its relationships with patient age and tumor stage. Methods: A cohort of 45 consecutive children with PNT diagnosed and treated at a single centre (2008-2014) with available primary tumor specimen at disease diagnosis and no prior chemotherapy was investigated. Immunohistochemistry for CD45, CD3, CD20, CD14, CD163, CD68, PDL1(P142), and FOXP3 was performed. Presence and status of immune infiltration were scored as follow: the presence of aggregates was assessed at 2.5X scanning magnification and recorded as "high" if present or "low" if no aggregates were visible. Patient age was categorized according to London WB et al (2005) using a 460 days cut-off and INSS tumor stage was considered. Results: Patient age ranged between 8 days and 14 years. Tumor infiltrating CD45 and CD3 scores were lower in INSS tumor stage 4 compared to other INSS tumor stages (CD45: OR=12.37, 95%CI 1.38 -171.00, P=0.01; CD3: OR=9.86, 95%CI 1.52-114.13; P<0.01). Similarly, the monocytes and macrophages markers CD163 and CD14 were associated with tumor INSS stage. The expression of these markers was significantly higher in patient older than 460 days (CD163: OR=4.41, 95%CI 0.77-32.12, P=0.03; CD14: OR=6.94, 95%CI 0.79-335.33, P<0.01). Interestingly, PD-L1 was detected only on immune cells but not on neuroblastic cells. Finally, Treg(FOXP3+) score was low in all but one case. Conclusions: Immune contexture in PNT significantly varies across patient age and tumor stage suggesting a role for maturity of immune system in these patients. [Table: see text]