The Immune System's Contribution to the Clinical Efficacy of EGFR Antagonist Treatment.
The Immune System's Contribution to the Clinical Efficacy of EGFR Antagonist Treatment.
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DOI：
10.3389/fphar.2017.00575
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发表时间：
2017
影响因子：
5.6
通讯作者：
Zaiss DMW
中科院分区：
文献类型：
--
作者：
MacDonald F;Zaiss DMW
表皮生长因子受体（EGFR）拮抗剂是最早开发的靶向受体酪氨酸激酶的抗癌治疗之一。然而，EGFR拮抗剂应用如何解释其在不同类型癌症中的临床疗效的潜在作用模式在很大程度上仍未得到解决。许多研究结果表明，EGFR拮抗剂治疗的大部分效应可能不是基于对肿瘤本身的直接影响。相反，它可能是基于间接效应，可能通过免疫系统介导。在这篇综述中，讨论了EGFR对免疫系统功能的作用，以及EGFR拮抗剂治疗如何通过阻断巨噬细胞和表达FoxP3的调节性CD4+ T细胞功能来影响肿瘤生长。基于这些发现，我们认为目前的治疗方案的影响，并建议新的方法，以提高疗效的EGFR拮抗剂治疗的未来。最后，我们提出了改善EGFR拮抗剂的潜在方法，以提高其临床疗效，同时减少不必要的副作用。
Epidermal Growth Factor Receptor (EGFR) antagonists were one of the first anti-cancer treatments developed targeting a Receptor Tyrosine Kinase. However, the underlying mode of action of how EGFR antagonist application can explain its clinical efficacy in different types of cancers remains largely unresolved. Numerous findings have suggested that a substantial portion of the effects attributed to EGFR antagonist treatment might not be based on direct influence on the tumor itself. Instead it may be based on indirect effects, potentially mediated via the immune system. In this review the role of the EGFR for the functioning of the immune system is discussed, alongside how EGFR antagonist treatment could be impacting tumor growth by blocking macrophage and FoxP3-expressing regulatory CD4+ T cell function. Based on these findings, we consider implications for current treatment schemes and suggest novel approaches to improve the efficacy of EGFR antagonist treatment in the future. Finally, we propose potential ways to improve EGFR antagonists, in order to enhance their clinical efficacy whilst diminishing unwanted side effects.
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DOI：
10.1084/jem.20090300
发表时间：
2009-06-08
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guerau-de-Arellano M;Martinic M;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
32.4
作者：
Joshi NS;Akama-Garren EH;Lu Y;Lee DY;Chang GP;Li A;DuPage M;Tammela T;Kerper NR;Farago AF;Robbins R;Crowley DM;Bronson RT;Jacks T
通讯作者：
Jacks T
影响因子：
45.3
作者：
Khambata-Ford, Shirin;Garrett, Christopher R.;Mauro, David J.
通讯作者：
Mauro, David J.
影响因子：
11.2
作者：
Maltby, Steven;Khazaie, Khashayarsha;McNagny, Kelly M.
通讯作者：
McNagny, Kelly M.
影响因子：
5.8
作者：
Garrido, Greta;Lorenzano, Pablo;Fernandez, Luis E.
通讯作者：
Fernandez, Luis E.