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DOI | 10.1002/2016GL071484 |
Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages | |
Guerriero, Jennifer L.1; Sotayo, Alaba1; Ponichtera, Holly E.1; Castrillon, Jessica A.1; Pourzia, Alexandra L.1; Schad, Sara1; Johnson, Shawn F.1; Carrasco, Ruben D.2; Lazo, Suzan1; Bronson, Roderick T.3; Davis, Scott P.4; Lobera, Mercedes4; Nolan, Michael A.4; Letai, Anthony1 | |
2017-03-16 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 543期号:7645页码:428-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects(1), but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition)(2,3) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies)(4,5) tumour-associated macrophages have had some success. We hypothesized that pharmacologic modulation of macrophage phenotype could produce an anti-tumour effect. We previously reported that a first-in-class selective class IIa histone deacetylase (HDAC) inhibitor, TMP195, influenced human monocyte responses to the colony-stimulating factors CSF-1 and CSF-2 in vitro(6). Here, we utilize a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumour microenvironment and reduces tumour burden and pulmonary metastases by modulating macrophage phenotypes. TMP195 induces the recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumours. Furthermore, combining TMP195 with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumour reduction. These data introduce class IIa HDAC inhibition as a means to harness the anti-tumour potential of macrophages to enhance cancer therapy. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000396337400052 |
WOS关键词 | CELLS ; PROGRESSION ; EXPRESSION ; THERAPY ; CANCER ; RESPONSES ; EFFICACY ; MODULATE ; DEFINES ; PROTEIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/28464 |
专题 | 气候变化 |
作者单位 | 1.Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA; 2.Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA; 3.Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA; 4.GlaxoSmithKline, 200 Technol Sq Suite 602, Cambridge, MA 02139 USA |
推荐引用方式 GB/T 7714 | Guerriero, Jennifer L.,Sotayo, Alaba,Ponichtera, Holly E.,et al. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages[J]. NATURE,2017,543(7645):428-+. |
APA | Guerriero, Jennifer L..,Sotayo, Alaba.,Ponichtera, Holly E..,Castrillon, Jessica A..,Pourzia, Alexandra L..,...&Letai, Anthony.(2017).Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages.NATURE,543(7645),428-+. |
MLA | Guerriero, Jennifer L.,et al."Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages".NATURE 543.7645(2017):428-+. |
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