Targeting tumor-associated macrophages to combat pancreatic cancer.
Targeting tumor-associated macrophages to combat pancreatic cancer.
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靶向肿瘤相关巨噬细胞对抗胰腺癌
DOI：
10.18632/oncotarget.9383
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发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Tan XL
中科院分区：
文献类型：
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作者：
Cui R;Yue W;Lattime EC;Stein MN;Xu Q;Tan XL
肿瘤微环境中充满了与肿瘤细胞一起进化并为肿瘤细胞向恶性转变提供支持的细胞。胰腺肿瘤微环境中免疫系统的劫持被认为是迄今为止各种化疗药物未能显著改善胰腺癌生存的原因。调节性T细胞、髓源性抑制细胞和成纤维细胞构成了一个复杂的生态微环境，它们可以抑制CD8+ T细胞和NK细胞，从而抑制效应免疫反应。肿瘤相关巨噬细胞（tumor associated macrophages， TAM）是一种多功能免疫细胞，在胰腺癌发展的不同阶段，对肿瘤微环境的刺激可以表达不同的功能程序。TAM与抑制抗肿瘤免疫反应、促进癌细胞增殖、刺激肿瘤血管生成和细胞外基质分解以及随后增强肿瘤侵袭和转移有关。许多新兴药物通过调节肿瘤微环境中的巨噬细胞来对抗其他类型的肿瘤，然而，对胰腺癌预防和治疗的研究却很少。更好地了解TAM在胰腺癌中的矛盾作用可能为新的预防和治疗方法铺平道路。本文就巨噬细胞的募集和分化、TAM与胰腺癌的进展和预后，以及与TAM相互作用的潜在预防和治疗靶点进行综述。
The tumor microenvironment is replete with cells that evolve with and provide support to tumor cells during the transition to malignancy. The hijacking of the immune system in the pancreatic tumor microenvironment is suggested to contribute to the failure to date to produce significant improvements in pancreatic cancer survival by various chemotherapeutics. Regulatory T cells, myeloid derived suppressor cells, and fibroblasts, all of which constitute a complex ecology microenvironment, can suppress CD8+ T cells and NK cells, thus inhibiting effector immune responses. Tumor-associated macrophages (TAM) are versatile immune cells that can express different functional programs in response to stimuli in tumor microenvironment at different stages of pancreatic cancer development. TAM have been implicated in suppression of anti-tumorigenic immune responses, promotion of cancer cell proliferation, stimulation of tumor angiogenesis and extracellular matrix breakdown, and subsequent enhancement of tumor invasion and metastasis. Many emerging agents that have demonstrated efficacy in combating other types of tumors via modulation of macrophages in tumor microenvironments are, however, only marginally studied for pancreatic cancer prevention and treatment. A better understanding of the paradoxical roles of TAM in pancreatic cancer may pave the way to novel preventive and therapeutic approaches. Here we give an overview of the recruitment and differentiation of macrophages, TAM and pancreatic cancer progression and prognosis, as well as the potential preventive and therapeutic targets that interact with TAM for pancreatic cancer prevention and treatment.