Abstract
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.
Highlights
Multiple myeloma (MM) is a malignant B-cell tumor characterized by the infiltration and proliferation of monoclonal plasma cells into the bone marrow
We evaluated the polarized functional status of bone marrow infiltrated by Tumor-associated macrophages (TAMs) by immunohistochemical staining of CD68, inducible nitric oxide synthase (iNOS), and CD163 in 240 patients with MM from January 2009 to December 2014
Twenty-nine (12.1 %) patients were in stage IA; 36 (15 %) patients were in stage IIA; 16 (6.7 %) patients were in stage IIB; 95 (39.6 %) patients were in stage IIIA; and 64 (26.7 %) patients were in stage IIIB at diagnosis according to the Durie– Salmon (DS) staging system
Summary
Multiple myeloma (MM) is a malignant B-cell tumor characterized by the infiltration and proliferation of monoclonal plasma cells into the bone marrow. This infiltration can result in excess immunoglobulin secretion, osteolytic lesions, impaired renal function, and myelosuppression [1]. Patient factors and tumor variables could influence the prognosis of myeloma. The International Staging System (ISS), the most widely used prognostic system for MM, stratifies patients into three groups based on serum albumin and β2-microglobulin www.impactjournals.com/oncotarget levels [3], which is well validated and applied; serum albumin and β2-microglobulin levels may not provide complete prognostic information because they do not incorporate tumor-microenvironment information
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
