Tumor Associated Macrophages in Kidney Cancer

Abstract

Tumor associated macrophages (TAMs) are an important element of tumor stroma. They originate from blood monocytes attracted by chemokines and cytokines produced by tumor cells and, being instructed by tumor microenvironment, develop into potent tumor-supporting cell population. TAMs were demonstrated to directly stimulate tumor cell proliferation and to promote angiogenesis. Further TAMs provide for efficient immune escape by producing immunosuppressive cytokines and facilitate tumor dissemination by producing extracellular matrix remodeling enzymes. In renal cell carcinoma (RCC), numerous studies were performed for elucidation of the role of TAM in tumor progression. Using pan-macrophages marker CD68 and type 2 macrophage (M2) markers CD163 and CD206, it was demonstrated that increased density of TAMs is associated with poor survival of patients. Although most of the studies are focused on M2 population in RCC, several markers rather typical for type 1 macrophages (M1) were also characterized. Macrophages isolated from RCC tumors were shown to produce proinflammatory cytokines TNFα, IL-1β, IL-6, and CCL2. It can be concluded that RCC is an excellent example of a tumor with hybrid phenotype of TAMs that share both M1 and M2 properties. Moreover, TAMs seem to be an attractive therapeutic target as well. Further investigations are needed for identification of RCC-specific TAM markers with high predictive capacity and/or suitable for therapeutic targeting.

A mosaic renal myeloid subtype with T-cell inhibitory and protumoral features is linked to immune escape and survival in clear cell renal cell cancer

“…An altered lipid metabolism is a characteristic of ccRCC (Pinthus et al, 2011;Rezende et al, 1999) as is the accumulation of immune complexes with accompanying complement activation, which is also seen in many inflammatory renal diseases (Bagavant and Fu, 2009;Nikolic-Paterson and Atkins, 2001). The identification of these complex features for a myeloid cell subtype enriched in RCC confirms and extends previous studies that have reported diametrically polarized macrophages in RCC tissue (Kovaleva et al, 2016).…”

Inflammatory response under zinc deficiency is exacerbated by dysfunction of the T helper type 2 lymphocyte–M2 macrophage pathway

“…Spleen sections (6 μm thick) were deparaffinized, washed in gently running tap water for 5 min (×1), and immersed in distilled water for 1 min (×2). Endogenous peroxidase activity was inactivated using 0·3% hydrogen peroxide, and the spleen sections were blocked for 50 min in Blocking One (Nacalai Tesque, Tokyo, Japan), washed twice for 5 min each in Tris‐buffered saline (TBS), and probed overnight with antibodies against ED1 (CD68, a marker of immature/general macrophages), ED2 (CD163, a marker of M2 macrophages), ED3 (CD169, a marker of M1 macrophages), IL‐4, IL‐13, or GATA‐3 (markers of Th2 lymphocyte‐related factors), and IFN‐ γ or T‐bet (markers of Th1 lymphocyte‐related factors). The antibodies and immune cell markers used in this study are listed in Table .…”

CD169‐positive sinus macrophages in the lymph nodes determine bladder cancer prognosis

“…[8][9][10] The number of TAM within the tumor is associated with advanced tumor progression in various cancers both in animal models and human patients. 8,11 In contrast, macrophages residing in the tumor-draining lymph nodes are important for enhancing anti-tumor immunity. 12 These macrophages are characterized by their surface expression of the CD169 + molecule and their localization at the interface between the tissue and circulating fluids.…”