Evaluation of M2/M1 macrophages presentations in neuroblastoma tumors

Abstract

Neuroblastoma is among fatal childhood diseases 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. In addition, high M1 infiltration was reported to be predominant in improved survival cases in some cancers. However, the prognosis significance of M2 in relation to M1 macrophages has not been well studied in neuroblastoma. In this study, we aimed to elucidate the comparative quantitation of M1 and M2 in association with patients’ survival expectation. To evaluate the predictive potential of M2/M1 ratio, we isolated TAMs from neuroblastoma tumors and quantified their biomarker gene expression using RT-qPCR. Observations showed that higher infiltration of M2 macrophages in tumor and lower infiltration of M1 macrophages were associated with higher risk in neuroblastoma. The M2/M1 ratio was remarkably higher in IR, whereas, cumulative gene expression of TAMs was higher in VL. Collectively, these data suggest that a higher ratio of M2/M1 polarized macrophages results in poorer survival from VL to IR, independently from total TAMs presence in tumors. This study supports auspicious treatment targeting an M1-populated polarization for survival improvement in neuroblastoma patients. Keywords: neuroblastoma, TAMs, M1/M2 macrophages, Very Low risk, Intermediate risk, survival, prognosis.