Abstract 707: Circulating immune profile in childhood neuroblastoma displays an activated response with simultaneous expression of checkpoint proteins by T cells and monocytes
Authors: Flavia B. Oliveira, Luísa M. Magalhães, Livia S. Passos, Joaquim C. Aguirre Neto, Álvaro P. Dutra, Patricia R. Martins, Paulo G. Oliveira Salles, Walderez O. Dutra, Kenneth J. Gollob
Journal: Cancer Research (2018)

Abstract Neuroblastoma (NB) is a rare childhood cancer typically affecting children under five and arising from neural crest sympathoadrenal linage cells. Despite its rarity, it is the most frequent solid tumor in children under five. Determination of the circulating immune response in childhood NB before treatment has begun can help in the identification of potential cells and pathways involved in disease development and suitability for immunotherapy. These studies were designed to investigate the cellular and soluble immune response (cytokines) using flow cytometry with peripheral blood samples in a group of seven NB patients and four non-NB solid tumor patients between the age of 20-42 months. These data of the systemic immune response were compared to the intensity of tumor infiltrating lymphocytes and disease outcome after 18 months of treatment. Analysis of peripheral blood cellular immune status revealed that the NB group displayed an increase in the frequency of effector memory T cells (p &amp;lt;0.05), as well as an increase in the expression of inhibitory molecules CTLA-4 and PD-1 by CD4 + T lymphocytes (p &amp;lt; 0.05), and CTLA-4 by CD8+ T cells (p &amp;lt;0.06). Moreover, an increase in PD-L2 was seen on transitional (CD14+CD16+) and non-classical (CD14-CD16+) monocytes from NB (p &amp;lt;0.05). Further studies analyzing circulating cytokines (IL-2, 4, 5, 6, 9, 10, 13, 17A, 17F, 21, 22, IFN-gamma and TNF-alpha) in the plasma of the same patients showed an overall pattern of increased cytokines from the NB group as compared to the control group with increased IL-5, IL-6, IL-9 and IL-10 (p &amp;lt; 0.10). Lastly, the NB group showed an intense tumor infiltrating lymphocyte response in both the septa region and tumor nests, which was correlated with circulating TNF-alpha levels (R2 = 0.82, p = 0.06). Overall these findings of the systemic immune response in this rare childhood cancer indicate an active immune response with profiles consistent with both a down modulatory response and an overall activated profile based on soluble cytokines and tumor infiltrating lymphocyte intensity. These findings point to a systemic immune-modulation profile of the cellular response associated with NB disease. Citation Format: Flavia B. Oliveira, Luísa M. Magalhães, Livia S. Passos, Joaquim C. Aguirre Neto, Álvaro P. Dutra, Patricia R. Martins, Paulo G. Oliveira Salles, Walderez O. Dutra, Kenneth J. Gollob. Circulating immune profile in childhood neuroblastoma displays an activated response with simultaneous expression of checkpoint proteins by T cells and monocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 707.