Significance of M2-Polarized Tumor-Associated Macrophage in Pancreatic Cancer

Kurahara, Hiroshi; Shinchi, Hiroyuki; Mataki, Yuko; Maemura, Kousei; Noma, Hidetoshi; Kubo, Fumitake; Shimada, Masahiko; Ueno, S.; Takao, Sonshin

doi:10.1016/j.jss.2009.05.026

Cited by 492 publications

(444 citation statements)

References 39 publications

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“…The p values were calculated by the log-rank test Macrophages derived from the CD34 ? bone marrow progenitors develop into monocytes, and extravasate into various tissues, where they differentiate into resident macrophages [15]. The monocyte-macrophage lineage is diverse and plastic, attributed to a complex transcriptome [30].…”

Section: Discussionmentioning

confidence: 99%

“…A handful of studies proved that the alternative activated M2 macrophages are the main infiltration files of TAMs in various tumors [15,16]. The M2-polarized macrophages promote tumor progression and metastasis by activating circuits that regulate tumor growth, adaptive immunity, stroma formation, and angiogenesis, and can be used as prognostic indicators [7,17,18].…”

Section: Introductionmentioning

confidence: 99%

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Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

et al. 2014

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Background Tumor-associated macrophages (TAMs), the most predominant tumor-infiltrating immune cells, are emerging prognostic factors and therapeutic targets for personalized therapy against malignant neoplasms. We aimed to evaluate the prognostic significance of diametrically polarized TAMs in gastric cancer and generate a predictive nomogram to refine a risk stratification system. Methods We evaluated polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68, CD11c, and CD206 in 180 consecutive gastric cancer patients from Zhongshan Hospital, Shanghai, China. Prognostic values were assessed in these patients. We created a predictive nomogram by integrating polarized TAMs with the TNM staging system for overall survival of gastric cancer patients.Results CD68 ? TAMs display polarized programs comprising CD11c ? proinflammatory macrophages (M1) and CD206 ? immunosuppressive macrophages (M2) that configure versatile infiltration files in gastric cancer. CD11c ? TAMs negatively correlated with lymph node metastasis (p = 0.012), whereas CD206 ? TAMs correlated with the Lauren classification (p = 0.031). No prognostic difference was observed for overall survival for CD68 density (high vs low, p = 0.1031), whereas high versus low CD11c density (p \ 0.0001) and low vs high CD206 density (p = 0.0105) indicate better overall survival. Multivariate Cox regression analysis identified CD11c and CD206 as independent prognostic factors (p \ 0.001 and p = 0.030, respectively), which could be integrated with the TNM staging system to generate a predictive nomogram for patient outcomes. Conclusion Infiltration of polarized TAMs, a novel identified independent prognostic factor, could be combined with the TNM stage to refine a risk stratification system and better stratify patients with different prognosis. Tipping TAMs to an antitumoral phenotype might be a promising therapeutic target for postoperative treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

et al. 2014

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“…Clinical studies suggest that the type of immunological profile expressed at the tumor site represents an independent prognostic factor. In particular, an established type-2 "suppressive" immunological profile correlates with poor prognosis, as shown in colorectal, hepatocellular and pancreatic carcinomas and in Hodgkin's lymphoma [61][62][63][64] Many studies have shed light on the intricate signalling network that drives myeloid cells towards M2-polarized activation. The acquisition of pro-tumoral M2 functions by TAM is driven by various cytokines and signals expressed within the tumor microenvironment [54].…”

Section: Tamcs Functionsmentioning

confidence: 99%

Origin and Functions of Tumor-Associated Myeloid Cells (TAMCs)

Sica

Porta

Morlacchi

et al. 2011

Cancer Microenvironment

100

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The construction of an inflammatory microenvironment provides the fuel for cancer development and progression. Hence, solid tumors promote the expansion and the recruitment of leukocyte populations, among which tumor-associated myeloid cells (TAMCs) represent a paradigm for cancer-promoting inflammation. TAMCs group heterogeneous phagocytic populations stemming from a common myeloid progenitor (CMP), that orchestrate various aspects of cancer, including: diversion and skewing of adaptive responses; immunosuppression; cell growth; angiogenesis; matrix deposition and remodelling; construction of a metastatic niche and actual metastasis. Several evidence indicate that TAMCs show plasticity and/or functional heterogeneity, suggesting that tumour-derived factors promote their functional "reprogramming" towards protumoral activities. While recent studies have attempted to address the role of microenvironment signals, the interplay between cancer cells, innate and adaptive immunity is now emerging as a crucial step of the TAMCs reprogramming. Here we discuss the evidence for the differentiation of TAMCs during the course of tumor progression and the molecular mechanisms that regulate such event.

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“…M1-like TAMs, however, are sparse and confined to the less hypoxic regions of tumors (15). The presence of M2-like TAMs in tumors correlates with poor prognosis (16,17), whereas the presence of M1-like TAMs correlates with longer survival for patients (18).…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation

Yin

Huang

Lynn

et al. 2013

Cancer Immunology Research

127

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Multiple tumor-derived factors are responsible for the accumulation and expansion of immune-suppressing myeloid-derived suppressor cells (MDSC) and M2-like tumor-associated macrophages (TAM) in tumors. Here, we show that treatment of tumor-bearing mice with docetaxel in combination with the phosphatidylserine-targeting antibody 2aG4 potently suppressed the growth and progression of prostate tumors, depleted M2-like TAMs, and MDSCs, and increased the presence of M1-like TAMs and mature dendritic cells in the tumors. In addition, the antibody markedly altered the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. In vitro studies confirmed that 2aG4 repolarized TAMs from an M2-to an M1-like phenotype and drove the differentiation of MDSCs into M1-like TAMs and functional dendritic cells. These data suggest that phosphatidylserine is responsible for the expansion of MDSCs and M2-like TAMs in tumors, and that bavituximab, a phosphatidylserine-targeting antibody currently in clinical trials for cancer, could reverse this process and reactivate antitumor immunity. Cancer Immunol Res; 1(4); 256-68. Ó2013 AACR.

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Significance of M2-Polarized Tumor-Associated Macrophage in Pancreatic Cancer

Cited by 492 publications

References 39 publications

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

Origin and Functions of Tumor-Associated Myeloid Cells (TAMCs)

Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation

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