肿瘤相关中性粒细胞的研究进展

肿瘤生长依赖肿瘤微环境,肿瘤相关中性粒细胞(TANs)是肿瘤微环境中的一种重要炎症细胞.TANs分为具有抗肿瘤效应的"N1"型和促肿瘤效应的"N2"型.因此,TANs具有对机体有利和有害的两面性.大量研究表明,TANs通过分泌细胞因子和化学因子等,影响肿瘤的生成、转移、血管生成与免疫调节.本文将从TANs的生物学特性和TANs与肿瘤发生发展、预后及治疗等方面,综述TANs和肿瘤关系的研究进展.     

癌相关成纤维细胞的异质性在靶向胰腺癌治疗中的角色

胰腺癌发病率逐年增高,但临床诊治进展有限,预后差。胰腺癌中肿瘤微环境(TME)与肿瘤侵袭转移和化疗耐药密切相关。癌相关成纤维细胞(CAF)是一种处于持续活化状态的成纤维细胞,是TME中最重要的细胞成分之一。CAF可通过多种分子介导的多种机制,促进胰腺癌的恶性生物学行为。而靶向CAF治疗胰腺癌疗效不佳,可能与胰腺癌中CA...     

肿瘤相关中性粒细胞与肿瘤的发生和发展

肿瘤微环境中除了肿瘤细胞外,还存在多种类型的其他细胞,包括基质细胞、内皮细胞和各种免疫细胞（如CD4+和CD8+T细胞、树突状细胞、NK细胞、巨噬细胞、中性粒细胞等）。近年来研究发现,肿瘤相关中性粒细胞（tumor-associated neutrophils, TANs）在肿瘤发生和发展中发挥着重要的作用。TANs可以通过多种机制促进肿瘤的生长和转移,这些机制包括TANs释放的弹性蛋白酶促进肿瘤增殖和转移,TANs分泌基质金属蛋白酶促进肿瘤血管的生成,同时高度活化的TANs也可杀伤肿瘤细胞起抗肿瘤的作用。对TANs的深入研究为肿瘤免疫提供了新的认识,以TANs及其分泌的一些分子作为靶点来调控TANs的功能,可能成为干预肿瘤发生、发展的重要方法。     

肿瘤相关中性粒细胞促进进展期胃癌淋巴结转移的临床病理研究

目的:探讨进展期胃癌(advanced gastric cancer, AGC)患者血液中性粒细胞、癌组织中肿瘤相关中性粒细胞(tumor-associated neutrophils, TANs)和淋巴结转移(lymph node metastasis, LNM)的关系。方法:回顾性分析125例AGC患者外周血中性粒细胞计数、中性粒细胞-淋巴细胞比值(neutrophil-lymphocyte ratio, NLR),以及肿瘤原发灶、癌栓、肿瘤引流淋巴结内TANs的分布,并探讨与LNM的关系;顺序选取39例AGC原发灶进行PD-L1免疫组化检测,探讨TANs与PD-L1表达的相关性。结果:肿瘤浸润深度、组织学低分化、有无脉管侵犯、TANs、NLR与LNM有显著相关性,外周血中性粒细胞计数与LNM无显著相关性。多因素分析显示,有无脉管侵犯(P=0.002)、组织学低分化(P=0.015)和TANs(P=0.003)是LNM的独立危险因素。同时发现原发灶TANs与PD-L1评分呈正相关。脉管内癌栓伴TANs组LNM比例(94.4%)呈现出高于癌栓不伴TANs组(80.5%)的趋势(P=0...     

肿瘤相关性中性粒细胞促肿瘤转移机制的研究进展

中性粒细胞是循环中最为丰富的白细胞，在机体的免疫反应中发挥重要作用。中性粒细胞不仅参与免疫反应，也在肿瘤的发生发展，特别是侵袭和转移过程中发挥重要作用。中性粒细胞可分化为N1和N2亚型，在肿瘤的转移中表现出抑制转移（N1）和促进转移（N2）两种截然不同的的作用。但肿瘤相关中性粒细胞（tumor-associated neutrophils，TANs）在肿瘤转移机制中发挥的作用相对比较复杂，尚缺乏系统阐述。本文主要介绍TANs，分析其在肿瘤转移过程中促进肿瘤发生侵袭和转移的机制，对TANs作为抗肿瘤治疗策略的可能性进行综述。      

肿瘤相关巨噬细胞在胃癌微环境中的作用

肿瘤微环境（TME）是肿瘤细胞及其周围的非肿瘤细胞和基质成分构成的复杂生态系统,包括免疫细胞、成纤维细胞和细胞外基质等多种成分。其中,肿瘤相关巨噬细胞（TAMs）是TME中的重要成分。TAMs是在TME中浸润并且聚集在恶性肿瘤细胞周围的巨噬细胞,是TME中最为重要的组成细胞之一,在肿瘤发生发展中发挥重要作用。TAMs可通过分泌细胞因子和外泌体等与TME中的其他细胞相互作用,导致免疫抑制型TME,促进肿瘤细胞增殖转移。文章重点讨论TAMs在胃癌TME中的生物学特征、在胃癌侵袭和转移中的作用、免疫耐药机制以及与其他细胞间的相互作用,以期为实现针对TAMs的胃癌靶向治疗提供思路。     

肿瘤相关成纤维细胞对于免疫细胞的调节作用研究现状

肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)和肿瘤浸润性免疫细胞是肿瘤微环境(tu-mor microenvironment,TME)中重要的组成成分.二者在肿瘤微环境中相互通信,在肿瘤的发生和发展中发挥着重要作用.CAFs具有很大的异质性,不同的CAFs亚群存在着不同的功...     

肿瘤相关巨噬细胞对恶性肿瘤临床预后和治疗的影响

肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)作为肿瘤微环境中(tumor microenvi-ronment,TME)的核心调控者在肿瘤的发生发展中具有重要作用.活化的肿瘤相关巨噬细胞可分化出具有不同活化状态和功能的M1型和M2型,M1型肿瘤相关巨噬细胞主要介导抗肿瘤免疫效应,...     

肿瘤相关巨噬细胞与结肠肿瘤微环境关系的研究进展

摘 要：肿瘤微环境（tumor microenvironment,TME）是肿瘤细胞与人体免疫系统相互作用的首要场所,包含肿瘤细胞、免疫细胞、间质细胞及其分泌的活性因子等,深深地影响着肿瘤的产生、发展和转移。巨噬细胞是非常可塑的细胞,TME中的巨噬细胞被称为肿瘤相关巨噬细胞（tumor-associated macrophages,TAMs）,在结肠癌发生发展的不同阶段,对TME的刺激能表达不同的功能。近年来TAMs在TME中的作用也得到了更多的关注。因此了解TAMs与结肠癌TME的关系,对深入研究TAMs在结肠肿瘤中的作用具有重要意义。全文对TAMs与结肠癌TME的关系进行综述,以期为深入探究TAMs在结肠癌中的作用提供新的线索。     

CAFs在胰腺癌肿瘤微环境中作用的研究进展

胰腺癌肿瘤微环境中癌相关成纤维细胞(cancer-associated fibroblasts, CAFs)具有促进胰腺癌组织增殖、侵袭、转移、血管生成、免疫抑制及耐药等作用,在胰腺癌的演变和进展中发挥了重要作用。由于CAFs的起源较多且具有表型和功能异质性,给靶向CAFs的抗肿瘤治疗带来了巨大挑战,但是探究CAFs与胰腺癌细胞的相互作用可以为日后靶向CAFs治疗胰腺癌提供帮助。本文将探究胰腺癌肿瘤微环境中CAFs的作用机制并对近些年来国内外有关CAFs对胰腺癌作用的相关文献进行综述。     

Sex-specific prognostic effect of CD66b-positive tumor-infiltrating neutrophils (TANs) in gastric and esophageal adenocarcinoma

Gastric Cancer - Tumor-associated neutrophils (TANs) have recently been identified as a relevant component of the tumor microenvironment (TME) in solid tumors. Within the TME TANs mediate either...     

Immuno-oncology-microbiome axis of gastrointestinal malignancy

Research on the relationship between the microbiome and cancer has been controversial for centuries. Recent works have discovered that the intratumor microbiome is an important component of the tumor microenvironment (TME). Intratumor bacteria, the most studied intratumor microbiome, are mainly localized in tumor cells and immune cells. As the largest bacterial reservoir in human body, the gut microbiome may be one of the sources of the intratumor microbiome in gastrointestinal malignancies. An increasing number of studies have shown that the gut and intratumor microbiome play an important role in regulating the immune tone of tumors. Moreover, it has been recently proposed that the gut and intratumor microbiome can influence tumor progression by modulating host metabolism and the immune and immune tone of the TME, which is defined as the immuno-oncology-microbiome (IOM) axis. The proposal of the IOM axis provides a new target for the tumor microbiome and tumor immunity. This review aims to reveal the mechanism and progress of the gut and intratumor microbiome in gastrointestinal malignancies such as esophageal cancer, gastric cancer, liver cancer, colorectal cancer and pancreatic cancer by exploring the IOM axis. Providing new insights into the research related to gastrointestinal malignancies.     

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

The immune microenvironment plays a crucial role in supporting tumor growth and metastasis. Tumor-associated macrophages (TAMs) and neutrophils (TANs) are essential components of this microenvironment and affect tumor growth and progression in almost all solid neoplasms. Furthermore, TAMs, TANs and tumor-infiltrating dendritic cells (TIDCs) are found to infiltrate specific distant organs to prepare them as a site for metastatic cell seeding, forming the pre-metastatic niche. The spleen was identified as a major reservoir and source of circulating and tumor infiltrating immune cells. However, discrepancies about its role in supporting tumor growth exist. Thus, here we investigated the role of splenectomy in primary tumor and metastatic growth, and in the formation of an inflammatory niche. In a murine 4T1 and E0771 breast and Panc02 pancreatic cancer model, our results show that while splenectomy reduces the number of infiltrating TAMs, TANs and TIDCs within primary tumors, it does not affect its growth. In line, fewer TAMs, TANs and TIDCs accumulate in the metastatic microenvironment after splenectomy. Interestingly though, this affected metastatic growth depending on the metastatic route/site. The number of hematogenous breast cancer lung metastases was reduced after splenectomy but no effect was observed in breast or pancreatic lymph node metastases. Moreover, we observed that the immune composition of the pre-metastatic niche in lungs of breast cancer bearing mice was altered, and that this could cause the reduction of metastases. Altogether, our results highlight that splenectomy affects the immune microenvironment not only of primary tumors but also of pre-metastatic and metastatic sites.     

Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment

Pancreatic cancer is known for its dismal prognosis despite efforts to improve therapeutic outcome. Recently, cancer nanomedicine, application of nanotechnology to cancer diagnosis and treatment, has gained interest for treatment of pancreatic cancer. The enhanced permeability and retention (EPR) effect that promotes selective accumulation of nanometer‐sized molecules within tumors is the theoretical rationale of treatment. However, it is clear that EPR may be insufficient in pancreatic cancer as a result of stromal barriers within the tumor microenvironment (TME). These limit intratumoral accumulation of macromolecules. The TME and stromal barriers inside it consist of various stromal cell types which interact both with each other and with tumor cells. We are only beginning to understand the complexities of the stromal barriers within the TME and its functional consequences for nanomedicine. Understanding the complex crosstalk between barrier stromal cells is challenging because of the difficulty of modeling pancreatic cancer TME. Here we provide an overview of stromal barriers within the TME. We also describe the preclinical models, both in vivo and in vitro, developed to study them. We furthermore discuss the critical gaps in our understanding, and how we might formulate a better strategy for using nanomedicine against pancreatic cancer.     

Mesenchymal stem cells in lung cancer tumor microenvironment: their biological properties,influence on tumor growth and therapeutic implications

The tumor microenvironment (TME) of lung cancer has been documented to play an important role in participating in tumor disease progression. As the precursor of most stroma in TME, mesenchymal stem cells (MSCs) draw great attention since evidence has suggested that MSCs derived from lung cancer patients present a different phenotype compared to their normal counterparts. Furthermore, MSCs could be recruited towards tumor sites and influence tumor survival, although the effect remains contradictory. Our review will summarize the current advance of the role MSCs in lung cancer and explore the possible treatment strategies by blocking their crosstalk.     

Prognostic significance of CD8+ tumor-infiltrating lymphocytes and CD66b+ tumor-associated neutrophils in the invasive margins of stages I–III colorectal cancer

Tumor-infiltrating immune cells play an essential role in cancer progression and may help supplement the Tumor, Node, Metastasis (TNM) classification for cancer prognosis. Currently, there are numerous conflicting reports discussing the significance of tumor-associated neutrophils (TANs) in colorectal cancer (CRC). In particular, the role of TANs in the invasive margin is unclear. The present study investigated the prognostic significance of CD66⁺ TANs and CD8⁺ tumor-infiltrating lymphocytes (TILs) in the invasive margin of 103 patients with CRC. By using immunohistochemistry, survival analysis was performed on CD8⁺ TILs and CD66⁺ TANs individually, as well as models including TILs and TANs simultaneously. The findings indicated that the densities of CD8⁺ TILs and CD66b⁺ TANs in the invasive margin may provide significant prognostic value for predicting survival. Moreover, the combined evaluation of CD8⁺ TILs and CD66b⁺ TANs in the invasive margin could further improve the validity for the prediction of oncological outcomes. In addition, multivariate analysis revealed that simultaneous low tumor infiltration by CD8⁺ TILs and CD66b⁺ was an independent predictive factor for overall survival (HR=4.17, 95% CI, 1.55-12.5; P=0.004) and disease-free survival (HR=2.75, 95% CI, 1.27-6.12; P=0.01). Given the importance of CD8⁺ TILs and CD66b⁺ TANs in the tumor microenvironment, the assessment of their densities in the invasive margin may serve as a valuable prognostic marker for CRC.     

Investigation of Nano-Bio Interactions within a Pancreatic Tumor Microenvironment for the Advancement of Nanomedicine in Cancer Treatment

Pancreatic cancer is one of the deadliest types of cancer, with a five-year survival rate of only 10%. Nanotechnology offers a novel perspective to treat such deadly cancers through their incorporation into radiotherapy and chemotherapy. However, the interaction of nanoparticles (NPs) with cancer cells and with other major cell types within the pancreatic tumor microenvironment (TME) is yet to be understood. Therefore, our goal is to shed light on the dynamics of NPs within a TME of pancreatic origin. In addition to cancer cells, normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were examined in this study due to their important yet opposite roles of suppressing tumor growth and promoting tumor growth, respectively. Gold nanoparticles were used as the model NP system due to their biocompatibility and physical and chemical proprieties, and their dynamics were studied both quantitatively and qualitatively in vitro and in vivo. The in vitro studies revealed that both cancer cells and CAFs take up 50% more NPs compared to NFs. Most importantly, they all managed to retain 70–80% of NPs over a 24-h time period. Uptake and retention of NPs within an in vivo environment was also consistent with in vitro results. This study shows the paradigm-changing potential of NPs to combat the disease.