Intratumoral immunosuppression profiles in 11q‐deleted neuroblastomas provide new potential therapeutic targets

High‐risk 11q‐deleted neuroblastomas display features of a higher immunosuppression microenvironment than other high‐risk neruoblastomas. Efficacy of current anti‐GD2 immunotherapy in 11q‐deleted neuroblastomas may be reduced by inhibition of effector cells by kynurenine production and tryptophan depletion by IDO1, polarized M2 macrophages, PD‐L1 expression, and IL‐10‐dependent Treg conversion from resting CD4+ T cells, providing a rationale for further combination immunotherapy studies. High‐risk neuroblastoma (NB) patients with 11q deletion frequently undergo late but consecutive relapse cycles with fatal outcome. To date, no actionable targets to improve current multimodal treatment have been identified. We analyzed immune microenvironment and genetic profiles of high‐risk NB correlating with 11q immune status. We show in two independent cohorts that 11q‐deleted NB exhibits various immune inhibitory mechanisms, including increased CD4+ resting T cells and M2 macrophages, higher expression of programmed death‐ligand 1, interleukin‐10, transforming growth factor‐beta‐1, and indoleamine 2,3‐dioxygenase 1 (P