文献精选 > 高引权威"肿瘤微环境"文献

The Tumor Microenvironment Innately Modulates Cancer Progression.

文献信息

DOI	10.1158/0008-5472.CAN-18-3962
PMID	31350295
期刊	Cancer research
发表年份	2019
被引次数	1808
关键词	肿瘤微环境, 癌症进展, 免疫细胞
文献类型	Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN	0008-5472
页码	4557-4566
期号	79(18)
作者	Dominique C Hinshaw, Lalita A Shevde

一句话小结

癌症的发展与周围基质的改变密切相关，癌细胞通过分泌多种因子重塑微环境，导致免疫细胞在肿瘤进展中发挥关键作用。研究揭示了癌细胞与免疫细胞的相互作用如何促进肿瘤生长，为改进治疗策略并靶向肿瘤微环境的多个组成部分提供了重要依据。

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肿瘤微环境 · 癌症进展 · 免疫细胞

摘要

癌症的发展和进展与周围基质的改变密切相关。癌细胞通过分泌各种细胞因子、趋化因子及其他因素，能够在功能上塑造其微环境。这导致周围细胞的重编程，使其在肿瘤的生存和进展中发挥决定性作用。免疫细胞是肿瘤基质的重要组成部分，并在这一过程中起着关键作用。越来越多的证据表明，先天免疫细胞（如巨噬细胞、中性粒细胞、树突状细胞、先天淋巴细胞、髓源性抑制细胞和自然杀伤细胞）以及适应性免疫细胞（如T细胞和B细胞）在肿瘤微环境中存在时，会促进肿瘤的进展。癌细胞与邻近免疫细胞之间的相互作用最终形成了一个有利于肿瘤生长和转移的环境。理解这种对话的本质将有助于改进疗法，同时靶向肿瘤微环境的多个组成部分，从而提高患者获得良好治疗结果的可能性。

英文摘要

Cancer development and progression occurs in concert with alterations in the surrounding stroma. Cancer cells can functionally sculpt their microenvironment through the secretion of various cytokines, chemokines, and other factors. This results in a reprogramming of the surrounding cells, enabling them to play a determinative role in tumor survival and progression. Immune cells are important constituents of the tumor stroma and critically take part in this process. Growing evidence suggests that the innate immune cells (macrophages, neutrophils, dendritic cells, innate lymphoid cells, myeloid-derived suppressor cells, and natural killer cells) as well as adaptive immune cells (T cells and B cells) contribute to tumor progression when present in the tumor microenvironment (TME). Cross-talk between cancer cells and the proximal immune cells ultimately results in an environment that fosters tumor growth and metastasis. Understanding the nature of this dialog will allow for improved therapeutics that simultaneously target multiple components of the TME, increasing the likelihood of favorable patient outcomes.

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主要研究问题

1. 肿瘤微环境中不同类型的免疫细胞如何具体影响肿瘤细胞的生长和转移？
2. 是否存在特定的细胞因子或化学因子在肿瘤微环境中起到关键调节作用？
3. 研究表明，肿瘤微环境如何影响肿瘤治疗的效果，特别是在免疫疗法方面？
4. 在肿瘤微环境的研究中，是否有新的治疗靶点被发现，能够改善患者预后？
5. 肿瘤微环境的变化如何影响肿瘤的异质性和耐药性，未来的研究方向是什么？

核心洞察

研究背景和目的

肿瘤微环境（TME）是肿瘤发展和进展的重要组成部分。肿瘤细胞通过分泌细胞因子和化学因子来重塑其周围微环境，调节免疫细胞的功能，从而促进肿瘤的生存和转移。本文旨在总结TME中先天免疫细胞（如巨噬细胞、中性粒细胞、树突状细胞等）如何促进癌症进展的机制，以及针对这些细胞的临床治疗策略。

主要方法/材料/实验设计

研究通过文献回顾的方式，分析了TME中各类免疫细胞的功能及其在肿瘤进展中的作用，尤其关注先天免疫细胞的相互作用及其在肿瘤微环境中的动态变化。

关键结果和发现

1. 巨噬细胞：巨噬细胞可被极化为M1（促炎）和M2（免疫抑制）两种表型，M2型巨噬细胞在肿瘤微环境中促进肿瘤生长，且其高浸润与不良预后相关。
2. 树突状细胞：树突状细胞在肿瘤微环境中表现出免疫耐受性，能够抑制T细胞反应，促进肿瘤进展。
3. 中性粒细胞：中性粒细胞在肿瘤早期表现为抗肿瘤（N1）表型，但在肿瘤进展过程中转变为促进肿瘤的N2表型。
4. 髓系抑制细胞（MDSC）：MDSC在TME中具有强大的免疫抑制功能，促进肿瘤细胞的干性和转移能力。

主要结论/意义/创新性

本文强调了TME中免疫细胞的复杂性及其在肿瘤进展中的关键作用。理解这些细胞的相互作用机制为开发新的多靶点治疗策略提供了基础，可能提高患者的治疗效果和预后。

研究局限性和未来方向

研究主要基于现有文献，缺乏临床数据的支持。未来的研究应集中于：

• 更深入地探索不同肿瘤类型中TME的特异性。
• 开发靶向免疫细胞的治疗方法，特别是针对MDSC和肿瘤相关巨噬细胞的干预策略。
• 考虑多种免疫细胞之间的相互作用，制定综合治疗方案。

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