干旱区生态环境知识资源中心(Arid): Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination

Arid

DOI	10.1038/s41591-020-1131-x
	Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination
	Yu, Jiali; Green, Michael D.; Li, Shasha; Sun, Yilun; Journey, Sara N.; Choi, Jae Eun; Rizvi, Syed Monem; Qin, Angel; Waninger, Jessica J.; Lang, Xueting; Chopra, Zoey; El Naqa, Issam; Zhou, Jiajia; Bian, Yingjie; Jiang, Long; Tezel, Alangoya; Skvarce, Jeremy; Achar, Rohan K.; Sitto, Merna; Rosen, Benjamin S.; Su, Fengyun; Narayanan, Sathiya P.; Cao, Xuhong; Wei, Shuang; Szeliga, Wojciech; Vatan, Linda; Mayo, Charles; Morgan, Meredith A.; Schonewolf, Caitlin A.; Cuneo, Kyle; Kryczek, Ilona; Ma, Vincent T.; Lao, Christopher D.; Lawrence, Theodore S.; Ramnath, Nithya; Wen, Fei; Chinnaiyan, Arul M.; Cieslik, Marcin; Alva, Ajjai; Zou, Weiping
通讯作者	Zou, WP (corresponding author), Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. ; Green, MD ; Zou, WP (corresponding author), Univ Michigan, Michigan Rogel Canc Ctr, Ctr Excellence Canc Immunol & Immunotherapy, Ann Arbor, MI USA. ; Green, MD (corresponding author), Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. ; Green, MD (corresponding author), Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. ; Zou, WP (corresponding author), Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. ; Zou, WP (corresponding author), Univ Michigan, Sch Med, Grad Program Immunol, Ann Arbor, MI USA. ; Zou, WP (corresponding author), Univ Michigan, Sch Med, Grad Program Canc Biol, Ann Arbor, MI USA.
来源期刊	NATURE MEDICINE
ISSN	1078-8956
EISSN	1546-170X
出版年	2021
卷号	27 期号:1 页码:152-+
英文摘要	Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. Patients with liver metastases derive limited benefit from immunotherapy independent of other established biomarkers of response. In multiple mouse models, we show that liver metastases siphon activated CD8(+) T cells from systemic circulation. Within the liver, activated antigen-specific Fas(+)CD8(+) T cells undergo apoptosis following their interaction with FasL(+)CD11b(+)F4/80(+) monocyte-derived macrophages. Consequently, liver metastases create a systemic immune desert in preclinical models. Similarly, patients with liver metastases have reduced peripheral T cell numbers and diminished tumoral T cell diversity and function. In preclinical models, liver-directed radiotherapy eliminates immunosuppressive hepatic macrophages, increases hepatic T cell survival and reduces hepatic siphoning of T cells. Thus, liver metastases co-opt host peripheral tolerance mechanisms to cause acquired immunotherapy resistance through CD8(+) T cell deletion, and the combination of liver-directed radiotherapy and immunotherapy could promote systemic antitumor immunity. Liver metastases reduce clinical and preclinical immune-checkpoint inhibitor efficacy through hepatic siphoning of circulating activated CD8(+) T cells, but therapeutic benefit can be improved by combining immunotherapy with liver-directed radiotherapy.
类型	Article
语种	英语
开放获取类型	Green Accepted
收录类别	SCI-E
WOS记录号	WOS:000604849400001
WOS关键词	DRAINING LYMPH-NODES ; CANCER-IMMUNITY ; BLOCKADE ; RADIATION ; MECHANISMS ; APOPTOSIS ; CONTACT ; PD-L1
WOS类目	Biochemistry & Molecular Biology ; Cell Biology ; Medicine, Research & Experimental
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology ; Research & Experimental Medicine
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/348073
作者单位	[Yu, Jiali; Li, Shasha; Wei, Shuang; Szeliga, Wojciech; Vatan, Linda; Kryczek, Ilona; Zou, Weiping] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA; [Yu, Jiali; Green, Michael D.; Li, Shasha; Lang, Xueting; Zhou, Jiajia; Bian, Yingjie; Jiang, Long; Wei, Shuang; Szeliga, Wojciech; Vatan, Linda; Kryczek, Ilona; Alva, Ajjai; Zou, Weiping] Univ Michigan, Michigan Rogel Canc Ctr, Ctr Excellence Canc Immunol & Immunotherapy, Ann Arbor, MI USA; [Green, Michael D.; Sun, Yilun; El Naqa, Issam; Jiang, Long; Sitto, Merna; Rosen, Benjamin S.; Mayo, Charles; Morgan, Meredith A.; Schonewolf, Caitlin A.; Cuneo, Kyle; Lawrence, Theodore S.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA; [Green, Michael D.; Ramnath, Nithya] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA; [Li, Shasha; Cieslik, Marcin] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA; [Sun, Yilun] Univ Michigan, Dept Biostat, Ann Arbor, MI USA; [Journey, Sara N.; Waninger, Jessica J.; Chopra, Zoey; Tezel, Alang...
推荐引用方式 GB/T 7714	Yu, Jiali,Green, Michael D.,Li, Shasha,et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination[J],2021,27(1):152-+.
APA	Yu, Jiali.,Green, Michael D..,Li, Shasha.,Sun, Yilun.,Journey, Sara N..,...&Zou, Weiping.(2021).Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination.NATURE MEDICINE,27(1),152-+.
MLA	Yu, Jiali,et al."Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination".NATURE MEDICINE 27.1(2021):152-+.