Frontiers in Cell and Developmental Biology (Apr 2022)
Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma
Abstract
The tumor microenvironment (TME) influences disease initiation and progression. Cross-talks of cells within TME can affect the efficacy of immunotherapies. However, a precise, concise, and comprehensive TME landscape in neuroblastoma (NB) has not been established. Here, we profiled the TME landscape of 498 NB-related patients on a self-curated gene list and identified three prognostic TMEsubgroups. The differentially expressed genes in these three TMEsubgroups were used to construct a genetic signature of the TME landscape and characterize three GeneSubgroups. The subgroup with the worst overall survival prognosis, the TMEsubgroup/GeneSubgroup3, lacked immune cell infiltration and received the highest scores of MYCN- and ALK-related signatures and lowest scores of immune pathways. Additionally, we found that the GeneSubgroup3 might be benefited from anti-GD2 instead of anti-PD-1 therapy. We further created a 48-gene signature, the TMEscore, to infer prognosis and validated it in three independent NB cohorts and a pan-cancer cohort of 9,460 patients. We did RNA-seq on 16 samples and verified that TMEscore was higher in patients with stage 3/4 than stage 1/2 diseases. The TMEscore could also predict responses for several immunotherapies. After adding clinical features, we found that the nomogram-based score system, the TMEIndex, surpassed the current risk system at predicting survivals. Our analysis explained TME at the transcriptome level and paved the way for immunotherapies in NB.
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