Innate and adaptive immune cells in the tumor microenvironment.

文献信息

DOI	10.1038/ni.2703
PMID	24048123
期刊	Nature immunology
影响因子	27.6
JCR 分区	Q1
发表年份	2013
被引次数	2295
关键词	肿瘤微环境, 免疫细胞, T细胞, 免疫逃逸, 免疫治疗
文献类型	Journal Article, Review
ISSN	1529-2908
页码	1014-22
期号	14(10)
作者	Thomas F Gajewski, Hans Schreiber, Yang-Xin Fu

一句话小结

本研究探讨了肿瘤细胞如何逃避宿主CD8(+) T细胞的免疫攻击，发现肿瘤微环境可分为两类：一类具有T细胞炎症表型，通过免疫抑制通路抵抗免疫攻击；另一类则缺乏这种表型，似乎通过免疫排斥或无知机制实现逃逸。这一发现为不同类型肿瘤的免疫治疗策略提供了重要依据，强调了针对肿瘤微环境特征实施个性化治疗的必要性。

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肿瘤微环境 · 免疫细胞 · T细胞 · 免疫逃逸 · 免疫治疗

摘要

大多数肿瘤细胞表达能够介导宿主CD8(+) T细胞识别的抗原。临床检测到的癌症必须已经逃避了抗肿瘤免疫反应才能得以逐渐生长。最近的研究表明，肿瘤逃逸可以根据肿瘤微环境的细胞和分子特征分为两大类。一类主要亚群显示出T细胞炎症表型，包含浸润的T细胞、广泛的趋化因子谱以及表明先天免疫激活的I型干扰素特征。这些肿瘤似乎通过免疫系统抑制通路的主导抑制效应抵抗免疫攻击。另一种主要表型缺乏这种T细胞炎症表型，似乎通过免疫系统的排斥或无知来抵抗免疫攻击。这两种主要的肿瘤微环境表型可能需要不同的免疫治疗干预，以实现最佳的治疗效果。

英文摘要

Most tumor cells express antigens that can mediate recognition by host CD8(+) T cells. Cancers that are detected clinically must have evaded antitumor immune responses to grow progressively. Recent work has suggested two broad categories of tumor escape based on cellular and molecular characteristics of the tumor microenvironment. One major subset shows a T cell-inflamed phenotype consisting of infiltrating T cells, a broad chemokine profile and a type I interferon signature indicative of innate immune activation. These tumors appear to resist immune attack through the dominant inhibitory effects of immune system-suppressive pathways. The other major phenotype lacks this T cell-inflamed phenotype and appears to resist immune attack through immune system exclusion or ignorance. These two major phenotypes of tumor microenvironment may require distinct immunotherapeutic interventions for maximal therapeutic effect.

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主要研究问题

核心洞察

研究背景和目的

肿瘤微环境中的免疫细胞在肿瘤的发生和发展中扮演着重要角色。肿瘤细胞通常表达抗原，可以被宿主的CD8+ T细胞识别。肿瘤能够持续生长的一个原因是它们逃避了抗肿瘤免疫反应。研究表明，肿瘤微环境的细胞和分子特征可以分为两大类：一种是T细胞浸润型，另一种是非T细胞浸润型。这项研究的目的是探讨这两种类型的肿瘤微环境及其对免疫治疗的影响。

主要方法/材料/实验设计

研究主要通过对人类肿瘤组织的免疫表型分析和小鼠模型的机制实验来进行。具体步骤如下：

关键结果和发现

肿瘤微环境的免疫表型：
- T细胞浸润型肿瘤表现出活化的CD8+ T细胞和多种趋化因子的表达，通常与良好的预后相关。
- 非T细胞浸润型肿瘤缺乏这种浸润，且通常具有更高的基质密度和抑制性免疫细胞。
免疫逃逸机制：
- T细胞浸润型肿瘤中的CD8+ T细胞虽然存在，但受到PD-L1、IDO等免疫抑制通路的抑制。
- 非T细胞浸润型肿瘤则通过免疫排斥或无知机制逃避免疫监视。
临床相关性：
- T细胞浸润型肿瘤的存在可能作为免疫治疗反应的预测生物标志物。
- T细胞浸润与临床预后之间存在显著关联。

主要结论/意义/创新性

研究揭示了肿瘤微环境中不同免疫表型的存在及其对免疫治疗的影响。T细胞浸润型肿瘤可能更适合于现有的免疫治疗策略，而非T细胞浸润型肿瘤可能需要新的干预措施来诱导免疫激活。这为未来的免疫治疗策略提供了重要的指导，强调了对肿瘤微环境特征的深入理解。

研究局限性和未来方向

局限性：
- 本研究主要基于肿瘤组织样本和小鼠模型，缺乏大规模临床试验数据的支持。
- 对不同肿瘤类型的免疫表型特征的普遍性需要进一步验证。
未来方向：
- 进一步研究不同免疫表型的肿瘤在免疫治疗中的反应，以开发更有效的治疗策略。
- 探索如何改变非T细胞浸润型肿瘤的微环境，以促进T细胞的浸润和活化。

参考文献

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... (2285 更多篇文献)

Innate and adaptive immune cells in the tumor microenvironment. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​