Prognostic significance of mast cell count following curative resection for pancreatic ductal adenocarcinoma

Cai, Shouwang; Yang, Shaoxing; Gao, Jie; Pan, Ke; Chen, Jiye; Wang, Yulan; Wei, Lixin; Dong, Jiahong

doi:10.1016/j.surg.2010.10.009

Cited by 72 publications

(54 citation statements)

References 35 publications

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“…Mast cells have been extensively studied in PDAC, where the degree of their infiltration was identified as a predictive marker of patient survival (39)(40)(41)(42) and correlated with lymph node metastases, tumor grade, microvessel density, and lymphatic and microvascular invasion (39,41,42); although their relevance in pancreatic tumorigenesis in animal models yielded somehow conflicting results, depending on the model used (40,43). Basophils in our study were the cells mainly responsible for the presence of IL4 in TDLNs of patients, where their percentage significantly correlated with IL4 expression and the ratio of Th2/Th1 lymphoid cells in the corresponding tumor.…”

Section: Discussionmentioning

confidence: 99%

Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients

et al. 2016

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In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates, comprised mainly of Th2 cells, predict a poor survival outcome in patients. IL4 signaling has been suggested to stabilize the Th2 phenotype in this setting, but the cellular source of IL4 in PDAC is unclear. Here, we show that basophils expressing IL4 are enriched in tumor-draining lymph nodes (TDLN) of PDAC patients. Basophils present in TDLNs correlated significantly with the Th2/Th1 cell ratio in tumors, where they served as an independent prognostic biomarker of patient survival after surgery. Investigations in mouse models of pancreatic cancer confirmed a functional role for basophils during tumor progression. The recruitment of basophils into TDLN relied partly upon the release of chemokine CCL7/MCP3 by "alternatively activated" monocytes, whereas basophil activation was induced by T-cell-derived IL3. Our results show how basophils recruited and activated in TDLNs under the influence of the tumor microenvironment regulate tumor-promoting Th2 inflammation in PDAC, helping in illuminating a key element of the immune milieu of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients

et al. 2016

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“…The deleterious roles of mast cells were identified in studies of neoplasms affecting the skin, including malignant melanoma (30,59,60), Merkel cell carcinoma (61), and primary cutaneous lymphoma (58). Increased numbers of mast cells were also found in pancreatic adenocarcinomas (62)(63)(64); squamous cell carcinomas (SCC) of the esophagus (65), mouth (66), and lip (67) (29, 30, 58-60, 62, 64-66, 71, 75), the extent of angiogenesis, as assessed by staining of microvessels (in most cases by immunohistochemistry using anti-human CD31 or CD34 antibodies), was positively correlated with the numbers of mast cells per unit area of tissue. In some of these studies, mast cells were shown to express VEGF (29,30).…”

Section: Studies Linking Mast Cells To Tumors In Humansmentioning

confidence: 99%

Mast Cells: Potential Positive and Negative Roles in Tumor Biology

Marichal

Tsai

Galli

2013

Cancer Immunology Research

153

150

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Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. Cancer Immunol Res; 1(5); 269-79. Ó2013 AACR. Disclosure of Potential Conflicts of InterestNo potential conflicts of interest were disclosed.

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“…Mast cells were originally thought to mediate type I hypersensitivity by releasing chemical mediators in allergic diseases [20]. Immunohistochemical analysis for the quantification of mast cells in pancreatic cancer revealed that the presence of higher numbers of mast cells in the intra-tumoral border zone was an independent prognostic factor for overall survival [21].…”

Section: Tissue Structure Of Pancreatic Cancer and Its Cellular Originmentioning

confidence: 99%

Inflammation and pancreatic cancer: disease promoter and new therapeutic target

2013

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Chronic inflammation has a certain impact on the carcinogenesis of the digestive organs. The characteristic tissue structure of pancreatic cancer, desmoplasia, results from inflammatory processes induced by cancer cells and stromal cells. Concerning the progression of pancreatic cancer, recent research has clarified the pivotal role of tumorstromal interaction, which promotes the development of an invasive phenotype of cancer and provides survival advantages against chemotherapeutic agents or immune surveillance. Tumor stromal cells such as pancreatic stellate cells and immune cells establish a microenvironment that protects cancer cells through complex interactions. The microenvironment of pancreatic cancer acts as a niche for pancreatic cancer stem cells from which therapy-resistance and disease recurrence develop. Inhibition of the stromal functions or restoration of the immune reaction against cancer cells has therapeutic benefits that enhance the efficacy of conventional therapies. Some of the recent advances in this field are now under evaluation in clinical settings, but many problems must be overcome to establish a radical therapy for pancreatic cancer. This review summarizes current knowledge about the tumor-promoting stromal functions, immune system modulation and therapeutic strategies targeting tumorstromal interactions in pancreatic cancer.

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Prognostic significance of mast cell count following curative resection for pancreatic ductal adenocarcinoma

Cited by 72 publications

References 35 publications

Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients

Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients

Mast Cells: Potential Positive and Negative Roles in Tumor Biology

Inflammation and pancreatic cancer: disease promoter and new therapeutic target

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