Tumor-associated macrophages as a prognostic parameter in multiple myeloma

Abstract

The interaction between multiple myeloma (MM) cells and the bone marrow stroma constitutes the basis of myeloma pathogenesis and has led the way for the corresponding therapeutic strategies. The aim of this study is to evaluate tumor-associated macrophages (TAMs) which is an important element of bone marrow stroma and its prognostic relevance in newly diagnosed MM patients. We also wanted to determine the association between TAMs and microvessel density (MVD). Sixty-eight patients, who were diagnosed with MM at the Department of Hematology, Gazi University Hospital, between January 2000 and January 2011, were reviewed retrospectively. Tumor-associated macrophages were evaluated by staining with anti-CD68 and anti-CD163 monoclonal antibodies, and MVD was evaluated by factor VIII staining. Median age was 60 (range, 40-84) years with 36 males and 32 females. The number of both CD 68+ and CD 163+ cells had a negative impact on OS at 6 years (p = 0.013 vs. 0.036; p = 0.015 vs. 0.039) in univariate and multivariate analysis in which age, sex, ISS, the induction treatment, and response to induction treatment are included as variables. High-grade MVD was found to be associated with increased CD163+ cell count. In conclusion, TAMs seems to be a promising prognostic histopathological marker in newly diagnosed MM patients.

The novel biomarker of alternative macrophage activation, soluble mannose receptor (sMR/sCD206): Implications in multiple myeloma

“…They also showed, that the bone marrow M infiltration was increased in MM patients, compared to samples from normal bone marrow and patients with monoclonal gammopathy of undetermined significance (MGUS) [24]. Further, higher M cell count in the bone marrow has been associated with shorter overall survival [5]. Taken together, these results, along with the data presented here, support the hypothesis that TAMs are indeed an important player in MM biology.…”

“…A subset of Ms called tumour-associated macrophages (TAMs) is now known to be important for development and progression of malignant diseases, due to suppression of anti-tumour immunity, promotion of angiogenesis, and facilitation of metastasis [2,3]. Further, infiltration by TAMs is associated with poor outcome in most human malignancies, including MM [4,5], and TAMs have been shown to promote MM cell resistance to chemotherapy in vitro and in vivo [6,7].…”

Preclinical validation of interleukin 6 as a therapeutic target in multiple myeloma

“…BMSCs able to release IL-6 into the extracellular space include tumor-associated macrophages (TAM), mast cells (MC), dendritic cells (DC), CD4 + or CD8 + T cells, osteoclasts (OC), osteoblasts and other cell types. An important source of IL-6 is TAMs, which are of prognostic importance in MM [112]. TAMs support myeloma cells [113] by releasing VEGF [114], a potent stimulator of angiogenesis in myeloma [115].…”

Dietary Consumption of Black Raspberries or Their Anthocyanin Constituents Alters Innate Immune Cell Trafficking in Esophageal Cancer

“…First, as shown in the plasma at weeks 15 and 25, BRBs, ACs, and PCA reduced blood vessel growth factor VEGF. In addition, as CD163 þ macrophages are associated with secreting cytokines that promote blood vessel formation (34,49), BRBs and their constituents may indirectly reduce angiogenesis in the esophagus by preventing CD163 þ cell accumulation in the tissue. Overall, results from the present study illustrate that BRBs, ACs, and PCA are capable of altering cytokine expression in the plasma and esophagi of NMBA-treated rats, which correlates à , Ãà , and ÃÃà significantly higher (P < 0.05, 0.01, and 0.001, respectively) than rats treated with NMBA and fed control diet.…”

“…Based on the literature, the markers CD68 and CD163 were used to mark macrophages, myeloperoxidase (MPO) for neutrophils, and CD161 as well as CD244 for NK cells (34)(35)(36)(37). Slides were deparaffinized, hydrated in water and individual antigens stained using a DAKO Autostainer Plus.…”