Iron deposition is associated with differential macrophage infiltration and therapeutic response to iron chelation in prostate cancer.
Iron deposition is associated with differential macrophage infiltration and therapeutic response to iron chelation in prostate cancer.
复制标题
DOI：
10.1038/s41598-017-11899-2
复制
发表时间：
2017-09-14
影响因子：
4.6
通讯作者：
Koutcher JA
中科院分区：
文献类型：
--
作者：
Leftin A;Zhao H;Turkekul M;de Stanchina E;Manova K;Koutcher JA
免疫细胞如巨噬细胞是大多数癌症的驱动因子和生物标志物。对肿瘤组织中的巨噬细胞浸润进行评分提供了与疾病结局和治疗反应相关的预后评估，但通常需要侵入性活检。在其他情况下，通过MRI在组织学和体内对巨噬细胞中含铁血黄素铁聚集体的常规检测表明，在癌症中进行类似的评估可以弥补我们评估肿瘤巨噬细胞浸润能力的差距。非血红素细胞铁的定量组织学和体内MRI评估显示，临床前前列腺肿瘤模型可以根据肿瘤和全身含铁血黄素铁积累进行区分。在FDA批准的铁螯合剂去铁酮的“标签外”给药期间监测细胞铁水平证明了肿瘤大小的显著减小，而没有对这些铁沉积物的广泛干扰。载铁浸润物的空间分布进一步证明，较高数量的浸润性巨噬细胞铁沉积物与较低的抗肿瘤螯合治疗反应相关。根据巨噬细胞的先天铁状态对巨噬细胞进行成像，为免疫肿瘤景观提供了新的表型窗口，并揭示了与巨噬细胞浸润和治疗结果相关的预后生物标志物。
Immune cells such as macrophages are drivers and biomarkers of most cancers. Scoring macrophage infiltration in tumor tissue provides a prognostic assessment that is correlated with disease outcome and therapeutic response, but generally requires invasive biopsy. Routine detection of hemosiderin iron aggregates in macrophages in other settings histologically and in vivo by MRI suggests that similar assessments in cancer can bridge a gap in our ability to assess tumor macrophage infiltration. Quantitative histological and in vivo MRI assessments of non-heme cellular iron revealed that preclinical prostate tumor models could be differentiated according to hemosiderin iron accumulation—both in tumors and systemically. Monitoring cellular iron levels during “off-label” administration of the FDA-approved iron chelator deferiprone evidenced significant reductions in tumor size without extensive perturbation to these iron deposits. Spatial profiling of the iron-laden infiltrates further demonstrated that higher numbers of infiltrating macrophage iron deposits was associated with lower anti-tumor chelation therapy response. Imaging macrophages according to their innate iron status provides a new phenotypic window into the immune tumor landscape and reveals a prognostic biomarker associated with macrophage infiltration and therapeutic outcome.
登录
查看更多内容
影响因子：
3.3
作者：
GILLIS, P;KOENIG, SH
通讯作者：
KOENIG, SH
影响因子：
2.5
作者：
Champy, Marie-France;Selloum, Mohammed;Auwerx, Johan
通讯作者：
Auwerx, Johan
DOI：
10.1056/nejmct1004810
发表时间：
2011-01-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brittenham GM
通讯作者：
Brittenham GM
DOI：
10.1186/1532-429x-16-40
发表时间：
2014-06-10
期刊：
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
影响因子：
--
作者：
Garbowski MW;Carpenter JP;Smith G;Roughton M;Alam MH;He T;Pennell DJ;Porter JB
通讯作者：
Porter JB
影响因子：
3.5
作者：
Cavey, Thibault;Ropert, Martine;Loreal, Olivier
通讯作者：
Loreal, Olivier