High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis

Yuan, Zhongyu; Luo, Rongzhen; Peng, Roujun; Wang, Shusen; Xue, Cong

doi:10.2147/ott.s61838

Cited by 171 publications

(141 citation statements)

References 29 publications

(27 reference statements)

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“…A number of studies have reported that high TAM levels within tumors were linked with local inflammation, angiogenesis, and poor prognosis for cancer patients (27,(42)(43)(44). The present study showed that high levels of scIgGs in breast tumors were also associated with high TAM levels.…”

Section: Elevated Sciggs Parallel Increased Levels Of Mmps In Breastsupporting

confidence: 69%

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Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity

Zhang

Deng

Fan

et al. 2015

Clinical Cancer Research

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Purpose: Studies have demonstrated that cancer-associated matrix metalloproteinases (MMP) can generate single peptide bond cleavages in the hinge region of immunoglobulin G 1 (IgG1). This study investigated the cleavage of endogenous IgGs by MMPs in the tumor microenvironment and the consequences of the IgG hinge cleavage for humoral immunity.Experimental Design: We investigated the occurrence of single peptide bond cleaved IgGs (scIgG) in tumor tissues and plasma samples collected from a cohort of breast cancer patients (n ¼ 60). Samples from healthy people (n ¼ 20) were used as the control. Antibody hinge cleavage was detected by multiple assays, including IHC, ELISA, and flow cytometry. A correlation analysis was conducted between scIgG levels and patient clinical parameters.Results: Levels of scIgGs in tumors were significantly higher than in normal tissues. In addition, scIgG levels in tumors were enriched compared with that in the plasma of the same patients. The appearance of scIgGs in tumor tissues was associated with altered host IgG content and decreased IgG1. Increased tumor scIgGs were found to be positively correlated with adverse clinical factors, such as elevated tumor-associated macrophages, increased expression of MMP9 and other MMPs, and local metastasis to axillary lymph nodes.Conclusions: The study contributes to mounting evidence for the presence of hinge-cleaved antibodies with reduced Fc immune effector function in the tumor microenvironment. The results highlight a link between tumor scIgGs and poor patient outcomes, and reveal a component of compromised humoral immunity within tumors that could point to new immunotherapeutic strategies to rescue host immunity. Clin Cancer Res; 21(23); 5380-90.Ó2015 AACR.

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Section: Elevated Sciggs Parallel Increased Levels Of Mmps In Breastsupporting

confidence: 69%

“…Several studies have indicated that TAMs promote tumor progression and are correlated with poor outcomes in cancer patients (26,27). TAMs are often attributed with the production of multiple cytokines and MMPs in the tumor microenvironment.…”

Section: Increased Sciggs Were Associated With High Macrophage Infiltmentioning

confidence: 99%

Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity

Zhang

Deng

Fan

et al. 2015

Clinical Cancer Research

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“…miR-223 was subsequently reported to promote the invasive potential of breast cancer cells (55 ). In agreement with that observation, a lower rate of overall survival was found in TNBC patients whose tumors had high concentrations of infiltrating TAMs (56 ). Although yet to be investigated, it is possible that exosomal miR-223 from the TAMs may be playing an adverse role here.…”

Section: Natural Killer (Nk) Cells Natural Killer T (Nkt) Cells Cd8supporting

confidence: 66%

The Role of Exosomes in Breast Cancer

2015

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BACKGROUND Although it has been long realized that eukaryotic cells release complex vesicular structures into their environment, only in recent years has it been established that these entities are not merely junk or debris, but that they are tailor-made specialized minimaps of their cell of origin and of both physiological and pathological relevance. These exosomes and microvesicles (ectosomes), collectively termed extracellular vesicles (EVs), are often defined and subgrouped first and foremost according to size and proposed origin (exosomes approximately 30–120 nm, endosomal origin; microvesicles 120–1000 nm, from the cell membrane). There is growing interest in elucidating the relevance and roles of EVs in cancer. CONTENT Much of the pioneering work on EVs in cancer has focused on breast cancer, possibly because breast cancer is a leading cause of cancer-related deaths worldwide. This review provides an in-depth summary of such studies, supporting key roles for exosomes and other EVs in breast cancer cell invasion and metastasis, stem cell stimulation, apoptosis, immune system modulation, and anti–cancer drug resistance. Exosomes as diagnostic, prognostic, and/or predictive biomarkers and their potential use in the development of therapeutics are discussed. SUMMARY Although not fully elucidated, the involvement of exosomes in breast cancer development, progression, and resistance is becoming increasingly apparent from preclinical and clinical studies, with mounting interest in the potential exploitation of these vesicles for breast cancer biomarkers, as drug delivery systems, and in the development of future novel breast cancer therapies.

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“…In tumor microenvironment, macrophages, so called tumor-associated macrophages (TAM), are commonly considered to have M2-macrophage phenotypes characterized as having a regenerative and pro-tumoral function, but not always (Bingle et al 2002, Mantovani et al 2002. Several epidemiological and clinical studies have shown that there are strong relationships between the high density of macrophages and the advanced stage or poor prognosis of various human cancers (Ryder et al 2008, Colvin 2014, Tiainen et al 2015, Yuan et al 2014. However, the opposite results have also shown that a high density of macrophages was associated with better overall survivals in colon (Funada et al 2003, Zhou et al 2010) and thyroid (Cunha et al 2012) cancers, suggesting that macrophages might have wide-raging biological actions in human cancers according to their own tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

CXCL16 signaling mediated macrophage effects on tumor invasion of papillary thyroid carcinoma

Cho¹,

Kim²,

Sun³

et al. 2015

Endocrine-Related Cancer

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Macrophages in tumor microenvironment have pivotal roles in tumor growth, metastasis, and angiogenesis. We investigated the interacting mechanism of macrophage actions in human papillary thyroid cancer (PTC). Co-cultures of macrophage/PTC significantly increased the cancer cell migration potentials, compared with the PTC culture alone. Treatment of conditioned medium (CM) of macrophage/PTC co-cultures enhanced cell invasions in 3D invasion assay. Cytokine array analysis demonstrated that CM of macrophage/PTC co-cultures contained a high level of CXCL16, while it was not found in CM of PTC culture alone. Treatment with CXCL16 enhanced the cell migration potentials in PTC cells, and blocking CXCL16 signaling using anti-CXCL16 antibody or metalloproteinase inhibitor (TAPI2) attenuated macrophagemediated enhancement of PTC cell migration potentials. In PTC cells, CXCL16 treatment or co-cultures with macrophages increased Akt phosphorylation, and these macrophagedependent increases of Akt phosphorylation was inhibited by anti-CXCL16 antibody. Moreover, Akt inhibitor attenuated macrophage-mediated increases of PTC cell migration potential. In macrophages, treatment of macrophage/PTC co-cultured CMs up-regulated CD163, Il10, and CD206, which were attenuated by anti-CXCL16 antibody treatment. Finally, CXCR6 and CXCL16 expressions were evaluated by immunohistochemical staining with a thyroid tissue microarray including 136 PTC. CXCR6 expressions showed positive correlation with the density of CD163 C macrophages and associated with lymph node metastasis. In conclusion, CXCL16 signaling partly mediated macrophage actions on PTC tumor cell invasion and also changed the macrophage phenotypes into M2-macrophages in PTC tumor microenvironment. These data suggested that CXCL16 signaling, a bidirectional player in macrophage-associated tumor microenvironment, might be a potential therapeutic target of human PTC.

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High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis

Cited by 171 publications

References 29 publications

Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity

Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity

The Role of Exosomes in Breast Cancer

CXCL16 signaling mediated macrophage effects on tumor invasion of papillary thyroid carcinoma

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