Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma

Komohara, Yoshihiro; Horlad, Hasita; Ohnishi, Koji; Fujiwara, Yukio; Suzu, Shinya; Eto, Masatoshi; Takeya, Motohiro

doi:10.1111/j.1349-7006.2011.01945.x

Cited by 227 publications

(231 citation statements)

References 43 publications

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“…Several previous studies also showed that PBMo-derived macrophages acquired M2 characteristics such as CD163, CD204, IL-10, VEGFA, and MMPs by conditioned medium of tumor cell line (TCM). 5,6,[35][36][37] We observed upregulation of various genes in the PBMo-derived macrophages stimulated with TECM by conducting a cDNA microarray analysis. As shown in Table 1, CXCL1, IL-6, and IL-8 are known to participate in tumor proliferation and angiogenesis.…”

Section: Gdf15 Increased the Growth Of The Escc Cell Lines By Triggermentioning

confidence: 99%

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

Urakawa

Utsunomiya

Nishio

et al. 2015

Laboratory Investigation

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Tumor-associated macrophages (TAMs) are known to be involved in the progression, angiogenesis, and motility of various cancers. We previously reported the association between an increased number of infiltrating TAMs with tumor progression and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To study the roles of TAMs in ESCC, we first exposed peripheral blood monocyte (PBMo)-derived macrophages from healthy volunteers to conditioned media of TE series human ESCC cell line (TECM) and confirmed the induction of the expression of the M2 macrophage marker CD204 and the protumorigenic factors interleukin (IL)-10, VEGFA, and MMPs. Next, we compared gene expression profiles between PBModerived macrophages stimulated with or without TECM by cDNA microarray and focused on growth differentiation factor 15 (GDF15) among the highly expressed genes including IL-6, IL-8, and CXCL1. Our immunohistochemical study of 70 surgically resected ESCCs revealed that GDF15 was present not only in cancer cells but also in macrophages. The high expression of GDF15 in the ESCCs was significantly correlated with several more malignant phenotypes including vessel invasion, lymph node metastasis, and clinical stages. Patients with high GDF15 expression showed significantly poorer disease-free survival (P = 0.011) and overall survival (P = 0.041). We also found that recombinant human GDF15 promotes cell proliferation and the phosphorylation of both Akt and Erk1/2 in ESCC cell lines in vitro. These results indicate that GDF15 is secreted by both TAMs and cancer cells in the tumor microenvironment and is associated with aberrant growth and a poor prognosis in human ESCC.

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Section: Gdf15 Increased the Growth Of The Escc Cell Lines By Triggermentioning

confidence: 99%

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

Urakawa

Utsunomiya

Nishio

et al. 2015

Laboratory Investigation

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“…10 Furthermore, high numbers of immune suppressive cells, such as regulatory T cells or myeloid derived suppressor cells (MDSC) in the peripheral blood and/or tumor lesions of RCC patients, were associated with a poor clinical outcome. 11,12 In order to increase the knowledge about the control and dynamics of immune responses directed against RCC, the immune cell phenotype of renal tumor lesions was characterized in this study. Flow cytometric analysis combined with immunohistochemistry was performed and correlated with tumor histology, Fuhrmann grading, tumor size, age of patients as well as patients' survival.…”

Section: Introductionmentioning

confidence: 99%

Immune signature of tumor infiltrating immune cells in renal cancer

et al. 2015

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Tumor-associated immune cells have been discussed as an essential factor for the prediction of the outcome of tumor patients. Lymphocyte-specific genes are associated with a favorable prognosis in colorectal cancer but with poor survival in renal cell carcinoma (RCC). Flow cytometric analyses combined with immunohistochemistry were performed to study the phenotypic profiles of tumor infiltrating lymphocytes (TIL) and the frequency of T cells and macrophages in RCC lesions. Data were correlated with clinicopathological parameters and survival of patients. Comparing oncocytoma and clear cell (cc)RCC, T cell numbers as well as activation-associated T cell markers were higher in ccRCC, whereas the frequency of NK cells was higher in oncocytoma. An intratumoral increase of T cell numbers was found with higher tumor grades (G1:G2:G3/4 D 1:3:4). Tumor-associated macrophages slightly increased with dedifferentiation, although the macrophage-to-T cell ratio was highest in G1 tumor lesions. A high expression of CD57 was found in T cells of early tumor grades, whereas T cells in dedifferentiated RCC lesions expressed higher levels of CD69 and CTLA4. TIL composition did not differ between older (>70 y) and younger (<58 y) patients. Enhanced patients' survival was associated with a higher percentage of tumor infiltrating NK cells and Th1 markers, e.g. HLA-DRC and CXCR3C T cells, whereas a high number of T cells, especially with high CD69 expression correlated with a worse prognosis of patients. Our results suggest that immunomonitoring of RCC patients might represent a useful tool for the prediction of the outcome of RCC patients.

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“…Immunostaining of human ccRCC specimens showed a correlation between the number of CD163+ M2 macrophages and age, sex, nuclear grade and TNM classification [88]. On the other hand, high levels of CD163+ cell infiltration were significantly associated with poor clinical prognosis in univariate but not multivariate analysis.…”

Section: Pro-tumoral Activity Of Csf-1r Signaling In Tammentioning

confidence: 82%

Colony-Stimulating Factor-1 Receptor in the Polarization of Macrophages: A Target for Turning Bad to Good Ones?

Rovida¹,

Sbarba²

2015

J Clin Cell Immunol

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Macrophages, which are found in all tissues, are an essential component of the innate immune system, and they play important roles in host defense, inflammation, autoimmune diseases as well as cancer. Functionally, macrophages are classified into two types: classically-activated M1 macrophages and alternatively-activated M2 macrophages. The M1 macrophages typically produce high levels of proinflammatory cytokines and chemokines, whereas M2 macrophages show an efficient phagocytic and scavenging activity. Because the phenotypes of polarized M1 and M2 macrophages can be induced, and reversed to some extent, by various signals, different phases of many diseases are associated with dynamic changes in the balance between M1 and M2 macrophages. The colony-stimulating factor 1 receptor (CSF-1R), a class III receptor tyrosine kinase, sustains the survival, proliferation and differentiation of monocytes and macrophages. Drugging CSF-1R may be the only way to target macrophages within a pathological context. However, CSF-1R-dependent signals may be either positive or detrimental depending on the disease and even on the phase of disease. The role of CSF-1R and its ligands, the colony-stimulating factor-1 and interleukin-34, in macrophages with respect to the pathogenesis of several inflammatory or neoplastic diseases has been reviewed previously. This review will focus specifically on evidences obtained about the role of CSF-1R in macrophage polarization in the context of physiological as well as pathological conditions including inflammation and cancer. The possibility to target CSF-1R, using the several inhibitors already available, for the treatment of inflammatory diseases as well as cancer will be also discussed.

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Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma

Cited by 227 publications

References 43 publications

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

Immune signature of tumor infiltrating immune cells in renal cancer

Colony-Stimulating Factor-1 Receptor in the Polarization of Macrophages: A Target for Turning Bad to Good Ones?

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