Prognostic value of diametrically polarized tumor-associated macrophages in multiple myeloma
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Xinyi Chen1,*, Jin Chen2,*, Wenyan Zhang3,*, Ruixue Sun1, Ting Liu1, Yuhuan Zheng1 and Yu Wu1
1Department of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, China
2Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
3Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
*These authors have contributed equally to this work
Yu Wu, email: [email protected]
Keywords: multiple myeloma; tumor-associated macrophages; overall response; prognosis; nomogram
Received: September 06, 2016 Accepted: June 26, 2017 Published: November 09, 2017
Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014. The overall response rates to chemotherapy were lower in patients with high CD68+ or CD163+ TAM densities than in those with low densities. Kaplan-Meier analysis showed that the progression-free survival (PFS, p = 0.001) and overall survival (OS, p < 0.001) of patients with low CD163+ TAM density were significantly higher than those of patients with high CD163+ TAM density. Furthermore, combined analysis of iNOS+ and CD163+ TAMs (iNOS/CD163 signature) exhibited greater power in predicting patient outcomes for both PFS (p < 0.001) and OS (p < 0.001). Moreover, Cox regression analysis identified iNOS+ and CD163+ TAMs as independent prognostic factors (p = 0.007, p < 0.001, respectively). These factors could be combined with the international staging system (ISS) to generate a predictive nomogram for patient outcomes. Our findings suggest that the mosaic of diametrically polarized TAMs is a novel independent prognostic factor that could be integrated into the evaluation of and therapy for MM.
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