ABSTRACT
Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.
ABSTRACT
Colorectal cancer is one of the most common causes of cancer death worldwide. In recent years, the number of patients with colorectal cancer has gradually increased. It has been proved that inflammation plays a special role in the occurrence and development of cancer. As important inflammatory cells, the role of neutrophils in tumors has gradually become research hotspots. It has been found that tumor-associated neutrophils can be polarized into pro-tumor and anti-tumor phenotypes in the tumor microenvironment, and have the ability to promote angiogenesis and tumor cell migration. This article reviews the role of tumor-associated neutrophils in the occurrence, development and metastasis of colorectal cancer, and the possibility of tumor-associated neutrophils as potential targets for cancer treatment.
ABSTRACT
The incidence rate of liver cancer keeps increasing in recent years, and this disease has difficulties in early diagnosis, poor treatment outcome, and poor prognosis. This article describes the research advances in tumor-associated neutrophils involved in the regulation of liver tumor microenvironment and points out that they can be used as a new target for the treatment of liver cancer. Combined with tumor-associated macrophages, regulatory T cells, and various cytokines in liver tumor microenvironment, tumor-associated neutrophils can achieve a systemic anti-tumor effect and thus bring hopes to the treatment of liver cancer.
ABSTRACT
Gastric cancer, which has very low 5-year survival rate, is a malignant tumor with high mortality around the world. In recent years, increasing attention has been paid to the effect of immunotherapy on cancer.Neutrophils in tumor immune microenvironment are associated with invasion, progression and prognosis of gastric cancer. Tumor-associated neutrophils can be classified into tumorsuppressor phenotype and tumorpromotion phenotype. Tumorsuppressor type can activate related cytokines to inhibit or kill tumor cells, while tumorpromotion type can secrete related chemical factors to promote the formation and progression of tumorand affect the prognosis of disease. This article reviews the mechanism of tumor-associated neutrophils in regulating the progression of gastric cancer.
ABSTRACT
Neutrophils are the most abundant leukocytes in the peripheral blood and play an important role in the immune response. However, there is growing evidence indicating that in addition to the immune response, neutrophils also have a crucial role in tumor development, especially in the process of invasion and metastasis. According to current research, depending on their phenotype, neu-trophils appear to be either anti-metastasis (N1) or pro-metastasis (N2). However, the role of tumor-associated neutrophils (TANs) in the metastasis of tumors is relatively complex and lacks a systematic introduction. This review mainly introduces TANs and focuses on the mechanism of TANs in promoting tumor invasion and metastasis. Finally, the possibility of TANs as an anti-tumor treatment strate-gy is discussed.
ABSTRACT
Lung cancer is a global disease with high morbidity and mortality, which seriously affects human health. The long-term existence of chronic pulmonary inflammation is closely related to the occurrence and development of lung cancer, neutrophils are not only involved in acute and chronic inflammation, but also in the composition of tumor microenvironment (TME), which is closely related to the occurrence and development of tumors. Recent studies have found that tumor-associated neutrophils (TANs) play an important role in the occurrence and development of lung cancer. This article reviews the role, mechanism and clinical significance of tumor-related neutrophils in lung cancer.
ABSTRACT
Objective:To investigate the prognostic significance of preoperative neutrophil-lymphocyte ratio(NLR)combined with tu-mor-associated neutrophils(TANs)in the stroma of gastric cancer tissues of patients.Methods:One hundred and twenty-six gastric cancer tissue samples from patients enrolled in Changhai hospital from June 2006 to May 2011 were divided into four groups accord-ing to NLRs in preoperative peripheral blood combined with high or low infiltration of neutrophils in gastric cancer tissues.The 5-year survival of the four groups was then compared,and their correlations with clinicopathologic features and prognosis were analyzed.Re-sults:High NLRs in peripheral blood combined with low infiltrating TANs in gastric tissues was associated with lower differential grade (P<0.001)and larger tumor size(P=0.026).Of the four groups,patients with high NLR in peripheral blood combined with low infiltrat-ing TANs in gastric cancer tissues demonstrated the lowest survival rates,whereas those with low NLR and high infiltrating TANs had highest survival rates, and this difference was statistically significant (P<0.05). Univariate and multivariate Cox regression analyses showed that high NLR in peripheral blood combined with low infiltrating TANs in gastric cancer tissues(P<0.05)was an independent factor indicating poor prognosis.Conclusions:NLR in preoperative peripheral blood combined with infiltrating TANs in gastric cancer tissues can be used as a prognostic indicator for patients with gastric cancer,especially high NLR in preoperative peripheral blood com-bined with low infiltrating TANs in gastric cancer tissue indicates poor prognosis.
ABSTRACT
Tumor growth depends on the tumor microenvironment(TME).Tumor-associated neutrophils(TANs)are important inflammatory cells in TME.TANs are divided intoN1type with anti-tumor effect andN2type of tumor-promoting effect.Therefore,TANs have both beneficial and harmful aspects of the body.A large number of studies have been shown that TANs affect tumor formation,metastasis,angiogenesis and immune response,regulated by the secretion of cytokines and chemokines.This review will summarize the biological characteristics of TANs,and tumor development,prognosis and treatment of tumor as well as research progress of the relationship between TANs and tumor.