Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy.
Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy.
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DOI：
10.1186/s40425-017-0257-y
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发表时间：
2017-07-18
影响因子：
10.9
通讯作者：
Rüttinger D
中科院分区：
文献类型：
--
作者：
Cannarile MA;Weisser M;Jacob W;Jegg AM;Ries CH;Rüttinger D
肿瘤相关巨噬细胞（TAM）的肿瘤允许和免疫抑制特性激发了对治疗靶向这些细胞的兴趣。在此背景下，集落刺激因子1（CSF 1）/集落刺激因子1受体（CSF 1 R）轴已获得最多的关注，目前正在临床开发各种靶向配体或受体的方法。关于CSF 1/CSF 1 R靶向药物耐受性的新数据表明其具有良好的安全性，使其成为标准治疗方式和免疫抑制剂的有吸引力的组合伙伴。这些药物的特异性及其有效的阻断活性已被弥漫型腱鞘巨细胞瘤（一种由CSF 1以自分泌方式驱动的良性结缔组织疾病）的显著缓解率所证实。在恶性疾病背景下，关于免疫疗法与CSF 1/CSF 1 R靶向剂组合的临床活性的数据尚待确定。随着我们对巨噬细胞生物学知识的扩展，很明显，巨噬细胞复杂的表型和功能特性受到其特定组织环境中连续的存活、分化、募集和极化信号的严重影响。因此，巨噬细胞在调节肿瘤发生中的作用以及消耗和/或重编程TAM作为癌症患者的治疗方法的影响可以根据这些细胞的器官特异性特征而变化很大。我们回顾了目前可用的CSF 1/CSF 1 R靶向药物的临床安全性和有效性数据，并提供了正在进行的临床研究的全面概述。此外，我们还讨论了局部组织巨噬细胞和肿瘤类型的特异性及其对未来CSF 1/CSF 1 R靶向治疗策略的潜在影响。
The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents. The specificity of these agents and their potent blocking activity has been substantiated by impressive response rates in diffuse-type tenosynovial giant cell tumors, a benign connective tissue disorder driven by CSF1 in an autocrine fashion. In the malignant disease setting, data on the clinical activity of immunotherapy combinations with CSF1/CSF1R-targeting agents are pending. As our knowledge of macrophage biology expands, it becomes apparent that the complex phenotypic and functional properties of macrophages are heavily influenced by a continuum of survival, differentiation, recruitment, and polarization signals within their specific tissue environment. Thus, the role of macrophages in regulating tumorigenesis and the impact of depleting and/or reprogramming TAM as therapeutic approaches for cancer patients may vary greatly depending on organ-specific characteristics of these cells. We review the currently available clinical safety and efficacy data with CSF1/CSF1R-targeting agents and provide a comprehensive overview of ongoing clinical studies. Furthermore, we discuss the local tissue macrophage and tumor-type specificities and their potential impact on CSF1/CSF1R-targeting treatment strategies for the future.
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肺泡巨噬细胞从胎儿单核细胞中发展，这些单核细胞在生命的第一周通过GM-CSF分化为长寿命细胞。
DOI：
10.1084/jem.20131199
发表时间：
2013-09-23
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guilliams M;De Kleer I;Henri S;Post S;Vanhoutte L;De Prijck S;Deswarte K;Malissen B;Hammad H;Lambrecht BN
通讯作者：
Lambrecht BN
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1084/jem.20151193
发表时间：
2016-10-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Afik R;Zigmond E;Vugman M;Klepfish M;Shimshoni E;Pasmanik-Chor M;Shenoy A;Bassat E;Halpern Z;Geiger T;Sagi I;Varol C
通讯作者：
Varol C
影响因子：
3.2
作者：
Gelhorn HL;Tong S;McQuarrie K;Vernon C;Hanlon J;Maclaine G;Lenderking W;Ye X;Speck RM;Lackman RD;Bukata SV;Healey JH;Keedy VL;Anthony SP;Wagner AJ;Von Hoff DD;Singh AS;Becerra CR;Hsu HH;Lin PS;Tap WD
通讯作者：
Tap WD
影响因子：
16.6
作者：
Bronte V;Brandau S;Chen SH;Colombo MP;Frey AB;Greten TF;Mandruzzato S;Murray PJ;Ochoa A;Ostrand-Rosenberg S;Rodriguez PC;Sica A;Umansky V;Vonderheide RH;Gabrilovich DI
通讯作者：
Gabrilovich DI