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与胰腺癌关系的研究进展

胰腺癌是一种起病隐匿、预后不良的消化系统恶性肿瘤,具有早期诊断困难、进展期生存时间短等特点。胰腺癌的肿瘤微环境(Tumor microenvironment, TME)中常常伴有大量免疫细胞的浸润,而肿瘤相关中性粒细胞(Tumor-associated neutrophils, TANs)作为TME的重要组成部分,在肿瘤的进程中起着重要作用。相关研究表明,TANs在胰腺癌的TME中发挥多种作用。本文从TANs与胰腺癌的关系进行综述,为理解胰腺癌发生机制与提出新疗法提供思路。     

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。      

肿瘤微环境与肿瘤

适宜的微环境可以引起基因组不稳定、提供支架和屏障、产生免疫豁免区域、诱导双向分化和形成许可微环境,促进肿瘤的发生.在肿瘤发展的过程中,肿瘤又形成组织缺氧、pH值降低、营养缺乏和肿瘤血管生成等特点的肿瘤微环境.肿瘤微环境既是肿瘤发生的原因又是肿瘤发展的结果.理解肿瘤微环境在肿瘤发生发展中的作用可能为肿瘤治疗提供新的策略.     

肿瘤相关成纤维细胞的代谢重编程与肿瘤进展的关系

肿瘤的生长并不完全由肿瘤细胞本身决定,肿瘤相关成纤维细胞(CAF)是肿瘤微环境的主要组成部分,在肿瘤的代谢、生长、转移、免疫逃逸和化疗耐药等方面具有重要作用。CAF的代谢重编程使其更倾向于有氧糖酵解,被称为"温伯格效应"。目前认为,CAF的代谢重编程调控机制可能与致癌基因c-myc、缺氧诱导因子1α和腺苷一磷酸(AMP)活化的蛋白激酶有关。代谢重编程的CAF可通过多种途径促进肿瘤的生长、发展:肿瘤微环境中的CAF可以通过分泌大量的细胞因子、趋化因子和促血管生成因子间接或直接调节肿瘤免疫;通过调节肿瘤间质液压、酸化肿瘤微环境,以及分泌可溶性因子促进肿瘤耐药;肿瘤组织中的CAF可募集抑制性免疫细胞,在肿瘤局部形成抑制性免疫微环境,促进上皮-间充质转化,激活肿瘤细胞增殖的信号通路从而促进肿瘤生长、耐药,形成恶性循环。阻断肿瘤、CAF和免疫微环境间的相互作用,可能成为未来肿瘤治疗的靶点。     

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,...     

肿瘤相关巨噬细胞在肿瘤进展中作用的研究进展

肿瘤相关巨噬细胞(TAM)是肿瘤微环境中重要的炎性细胞,在肿瘤基质中占有很大比例.在各种不同刺激因子的作用下,TAM可分化为经典活化型(M1)和交替活化型(M2)两种.M1-TAM具有抑制恶性肿瘤活性的作用,M2-TAM具有促进恶性肿瘤生长转移的作用.研究表明,肿瘤组织中的TAM主要为M2型,可分泌多种细胞因子和趋化因子,从而促进肿瘤新生血管生成及淋巴管生成,增强肿瘤细胞的侵袭和迁移能力,降低机体对肿瘤的免疫抑制作用.本文对TAM的表型及其在肿瘤进展中作用机制进行综述.     

肿瘤相关成纤维细胞在乳腺癌中的研究进展

肿瘤组织是肿瘤细胞、基质细胞和细胞外基质的复合体,它们构成了一个无序、具有攻击性的微环境,在肿瘤的发生发展中起着不可或缺的作用。在乳腺癌中,肿瘤相关成纤维细胞（CAF）不仅促进肿瘤的发生、增殖、浸润、转移和耐药,同时参与血管生成、淋巴管生成、细胞外基质重塑、重构微环境等诱发癌症的事件。因此,靶向CAF为肿瘤治疗提供了新...     

肿瘤相关巨噬细胞在鼻咽癌中的研究进展

肿瘤相关巨噬细胞(tumor-associated?macrophages,?TAMs)是肿瘤微环境中重要的免疫细胞,主要分为两种类型,即经典活化的M1型巨噬细胞和替代性活化的M2型巨噬细胞.TAMs在许多肿瘤组织中发挥M2型作用,即促进肿瘤的增殖、血管生成,诱导肿瘤细胞侵袭和转移,目前有关肿瘤相关巨噬细胞与肿瘤细胞之...     

抗肿瘤血管生成,肿瘤免疫治疗与肿瘤微环境的研究进展

抗肿瘤血管生成已是临床上肿瘤治疗的常用方法.但是,在此治疗过程中,肿瘤也会逐渐对抗血管生成药物产生耐药,这可能与肿瘤微环境的改变有关.怎样进一步改善抗肿瘤血管生成治疗疗效是目前的热点问题.最近有研究认为将其与肿瘤免疫治疗相联合可能是一种相互增益的治疗策略.本文就抗肿瘤血管生成治疗及其耐药、肿瘤微环境与肿瘤免疫治疗的关系,抗肿瘤血管治疗联合肿瘤免疫治疗的最新进展,进行综述.以期为今后探索肿瘤治疗新靶点、寻找肿瘤治疗新模式提供思路及参考依据,从而最终造福于广大癌症患者.     

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...     

Microenvironment Analysis of Prognosis and Molecular Signature of Immune-Related Genes in Lung Adenocarcinoma

There is growing evidence on the clinical significance of tumor microenvironment (TME) cells in predicting prognosis and therapeutic effects. However, cell interactions in tumor microenvironments have not been thoroughly studied or systematically analyzed so far. In this study, 22 immune cell components in the lung adenocarcinoma (LUAD) TME were analyzed using gene expression profile from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The TME-based molecular subtypes of LUAD were defined to evaluate further the relationship between molecular subtypes, prognosis, and clinical characteristics. A TME risk score model was constructed by using the differentially expressed genes (DEGs) of molecular subtypes. The relationship between the TME score and clinical characteristics and genomic mutations was compared to identify the genes that have significant associations with the TME. The comprehensive analysis of the TME characteristics may be helpful in revealing the response of LUAD patients to immunotherapy, providing a new strategy for immunotherapy.     

肿瘤相关中性粒细胞的异质性及潜在的临床意义

恶性肿瘤组织中肿瘤相关中性粒细胞（TAN）是肿瘤微环境的重要组成部分。TAN在肿瘤中的作用具有两面性。一方面,TAN可直接杀伤肿瘤细胞,或介导其他免疫细胞协同抗肿瘤。另一方面,TAN也可促进肿瘤血管生成、重塑细胞外基质及参与肿瘤细胞免疫逃逸。以上TAN功能的异质性是其在肿瘤微环境中多种复杂机制的交互调控下形成的,对肿瘤的发展或抑制产生重要的作用。因此,阐明TAN的异质性、不同亚群转化机制及其潜在的临床意义显得尤为重要,不仅有助于开发针对促肿瘤型中性粒细胞亚群的抑制类药物和疗法,还可进一步促进免疫治疗更多获益人群的新评估标准建立和筛选。     

Evaluating prognostic value and relevant gene signatures of tumor microenvironment characterization in esophageal carcinoma

BackgroundTumor microenvironment (TME) cells are an important part of tumor tissues. There is increasing evidence that the TME plays a vital role in tumor prognosis, and is associated with patient survival in various kinds of malignances. To date, very little research has been conducted on how to effectively use TME to better evaluate the prognosis of patients with esophageal carcinoma (EC). The concept of a “TME score” was introduced to better distinguish the prognosis of patients.MethodsWe employed bioinformatic methods to investigate the TME infiltration patterns of 160 patients with EC from the Cancer Genome Atlas (TCGA) cohort. TME clusters were identified using k-means clustering methods with 1,000 resampling times. The significance of the survival difference among patients belonging to different TME clusters was assessed by the log-rank test and Kaplan-Meier survival curves. Correlations between immune cell types and survival were calculated by a Cox regression, and the Pearson correlation coefficient (PCC) was used to measure the relationship among different immune cell types. We classified patient into 2 subtypes based on the optimal breakpoint of TME score determined by R package maxstat.ResultsTwo TME phenotypes were defined based on the immune cell type fractions, and patients with a high TME score phenotype had a better prognosis than those with a low TME score phenotype. Kaplan-Meier analysis for differentially expressed micro ribonucleic acids (RNAs) and messenger RNAs also showed that different TME score subtypes were significantly associated with the prognosis of EC. Just as tumor mutational burden can predict the efficacy of immunotherapy, the TME score can predict the efficacy of immune checkpoint inhibitors (ICIs). The genomic alterations of 2 TME score subtypes of EC further revealed that genomic instability is prevalent in TMEs, and patients with a low TME score subtype have a more unstable chromosome status than those with a high subtype.ConclusionsThus, TME score is an emerging prognostic biomarker for predicting the efficacy of ICIs.     

CAR-T细胞治疗突破实体肿瘤微环境新策略的研究进展

免疫治疗可通过提高患者自身免疫力以达到抗肿瘤目的,其中嵌合型抗原受体修饰T细胞(chimeric antigen receptor modified T cells,CAR-T)在血液系统肿瘤中已显现出良好疗效。实体肿瘤微环境(tumor microenvironment,TME)中免疫抑制细胞及分子等可限制CAR-T细胞在肿瘤部位浸润及其在浸润部位产生细胞毒作用。因此CAR-T细胞治疗在血液系统肿瘤中的显著疗效未在实体肿瘤中呈现。本文就如何突破TME限制,提高CAR-T细胞归巢能力及细胞毒作用,从而提高其在实体瘤中的疗效做一综述。     

Regulatory T cells: Their role in triple-negative breast cancer progression and metastasis

Triple-negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. This tumorigenicity is independent of hormonal or HER2 pathways because of a lack of respective receptor expression. TNBC is extremely prone to drug resistance and early recurrence because of T-regulatory cell (Treg) infiltration into the tumor microenvironment (TME) in addition to other mechanisms like genomic instability. Tumor-infiltrating Tregs interact with both tumor and stromal cells as well as extracellular matrix components in the TME and induce an immune-suppressive phenotype. Hence, treatment of TNBC with conventional therapies remains challenging. Understanding the protective mechanism of Tregs in shielding TNBC from antitumor immune responses in the TME will pave the way for developing novel, immune-based therapeutics. The current review focuses on the role of tumor-infiltrating Tregs in tumor progression and metabolic reprogramming of the TME. The authors have extended their focus to oncotargeting Treg-mediated immune suppression in breast cancer. Because of its potential role in the TME, modulating Treg activity may provide a novel strategic intervention to combat TNBC. Both under laboratory conditions and in clinical trials, currently available anticancer drugs and natural therapeutics as potential agents for targeting Tregs are explored.     

溶血磷脂信号在上皮性卵巢癌微环境中作用的研究进展

卵巢癌是妇科恶性肿瘤死亡的主要原因,发生在肿瘤微环境(TME)中的包括脂质代谢改变在内的代谢重编程是其主要特征。脂质中的几种溶血磷脂（也称癌脂）如溶血磷脂酸（LPA)是TME的重要组成部分,参与了肿瘤发生、发展的各个方面。本文综述了上皮性卵巢癌（EOC）TME中脂质代谢的改变,包括脂肪酸氧化增强、其它几种脂肪酸含量的改变,其次是溶血磷脂信号在EOC中的研究进展,重点介绍了LPA在EOC的TME中的作用:促进卵巢癌细胞的增殖、削弱免疫监测、侵袭转移、对化疗药物的抵抗等。