The prognostic value of tumor-associated macrophages in Non-Hodgkin's Lymphoma: A systematic review and meta-analysis.

Tumor-associated macrophages (TAMs) play an important role in the tumor environment, and were reported to be associated with poor prognosis in several tumors. However, the prognostic significance of TAMs in Non-Hodgkin's Lymphoma(NHL) remains controversial. Consequently, we aimed to evaluate the relationship between subpopulations of TAMs and clinical outcomes in NHL patients METHODS: We did a comprehensive search of the PubMed, ELSEVIER ScienceDirect, and Cochrane databases and extracted hazard ratio (HR) and their corresponding 95% confidence intervals (95% CIs) from eligible studies. Pooled total effect value by the STATA statistical software and analyzed correlation of TAMs with overall survival (OS) and progression-free survival (PFS). Furthermore, subgroup analysis and sensitivity analysis were also conducted.We deemed eleven studies, including 1211 NHL patients. Our study demonstrated that high-density CD68 TAMs is associated with poor OS (HR: 1.17; 95% CI, 0.81-1.54; P=0.000) and poor PFS (HR: 1.15; 95% CI, 0.63-1.67; P=0.000) compared with low-density CD68 TAMs in the tumor microenvironment. Similarly, high-density CD163 TAMs can also predict poor OS (HR: 1.52; 95% CI, 1.11-1.92; P=0.000) and shorter PFS (HR: 1.52; 95% CI, 0.73-2.30; P=0.000). In addition, the high CD163 /CD68 TAMs ratio is significantly correlated with poor OS (HR: 3.59; 95% CI, 0.77-6.40; P=0.013). However, in our subgroup analysis, high-density CD68 TAMs in the tumor microenvironment is associated with better OS (HR: 0.75; 95% CI, 0.41-1.09; P=0.000) in NHL patients treated with rituximab chemotherapy.Our results suggest that TAMs is a robust predictor of outcomes in NHL.