Relationship of tumour-associated macrophages with poor prognosis in Wilms’ tumour

Abstract

Wilms' tumour (WT) is the most common childhood renal tumour. Tumour-associated macrophages (TAMs) are a critical component of tumour microenvironments and contain two main subtypes, classically (M1) or alternatively (M2) activated macrophages. Evidence has revealed TAMs in predicting poor prognosis in some malignant tumours. However, the role of TAMs in WT is still unclear, and the relationship of different types of TAMs with prognosis has not been elucidated. The aim of the study was to explore the presence of two types of TAMs in WT and analyse the relationship of TAMs with prognosis. Overall, 61 paediatric patients with WT underwent nephrectomy before any chemotherapy from April 2006 to March 2014. The tumour tissues were analysed by Western blot, immunohistochemistry, and immunofluorescence to explore the distribution of M1 and M2 macrophages in different stages. Kaplan-Meier analysis with regard to the relationship between the presence of TAMs and follow-up information was performed. In the 61 patients (44 males and 17 females), there was a median age of 19 months (IQR 13-35.5); 47 patients are still alive, 11 died, 3 were lost to follow-up. According to the National Wilms Tumor Study (NWTS)-5 guidelines, the distribution of tumour stages was as follows: stage I, 27 patients; stage II, 18 patients; and stage III, 16 patients. The Western blot analysis showed that the density of M1 and M2 macrophages in tumour tissues were significantly greater than that in adjacent normal tissues. Immunohistochemistry showed the proportion of patients with positive M1-type macrophages across different stages: stage I, 66.7% (18/27); stage II, 44.4% (8/18); and stage III, 25% (4/16) (p=0.027). The proportion of patients with positive M2-type macrophages across different stages: stage I, 25.9% (7/27); stage II, 55.6% (10/18); and stage III, 81.3% (13/16) (p=0.002). Kaplan-Meier analysis suggested that patients with high densities of M2-type macrophages had shorter overall survival time than those with low densities (log-rank test, p=0.011). TAMs play a pivotal comments in the tumour microenvironment and tumorigenesis. With the progression of clinical stage, M2 macrophage densities increased greatly, and M1 macrophage density decreased. M2 macrophages represent a poor prognosis and can be utilized as a new indicator in pathological examination. There is a high density of TAMs in WT, and M2-type macrophage density increases with tumour progression and implies a poor prognosis.