A High M1/M2 Ratio Is Associated with Better Survival in Neuroblastoma

Abstract

Neuroblastoma is a fatal childhood disease that only 30% are long-term survival for high-risk cases. Tumor-associated macrophages (TAMs) play a crucial role in cancer development. TAMs are classified into classical activated M1 phenotype and alternative activated M2 phenotype under specific stimuli in tumor microenvironment. While M1 macrophages induce pro-inflammation and tumoricidal activity, M2 macrophages promote tumor progression. The poor survival of several cancers (including neuroblastoma) has been assigned to high M2 macrophages presentation. Meanwhile, studies on some cancers reported high M1 infiltration was associated with improved survival. However, the contribution of M1 macrophages has not been well studied in neuroblastoma. In this study, we aimed to elucidate the ratio of M1/M2 macrophages in association with patients ‘survival expectation. To evaluate activation status of M1 and M2 macrophages, we isolated TAMs from neuroblastoma tumors and quantified their biomarker gene expression using RT-qPCR. A remarkably high infiltration of M1 macrophages in tumor was observed with high event-free survival (EFS) and very low risk. Meanwhile, an M2-populated polarization was the status in poor outcome cases. Collectively, these data suggested that a higher ratio of M1/M2 polarized macrophages resulted in better survival from Very-Low risk (VL) to Intermediate- risk (IR). This study supports promising treatment targeting TAMs polarization for survival improvement in neuroblastoma patients.