干旱区生态环境知识资源中心(Arid): Lighting up the fire in cold tumors to improve cancer immunotherapy by blocking the activity of the autophagy-related protein PIK3C3/VPS34

Arid

DOI	10.1080/15548627.2020.1815439
	Lighting up the fire in cold tumors to improve cancer immunotherapy by blocking the activity of the autophagy-related protein PIK3C3/VPS34
	Janji, Bassam; Hasmim, Meriem; Parpal, Santiago; De Milito, Angelo; Berchem, Guy; Noman, Muhammad Zaeem
通讯作者	Janji, B ; Noman, MZ
来源期刊	AUTOPHAGY
ISSN	1554-8627
EISSN	1554-8635
出版年	2020
卷号	16 期号:11 页码:2110-2111
英文摘要	Cancer immunotherapy based on Immune checkpoint blockade (ICB) is a promising strategy to treat patients with advanced highly aggressive therapy-resistant tumors. Unfortunately, the clinical reality is that only a small number of patients benefit from the remarkable clinical remissions achieved by ICB. Experimental and clinical evidence claimed that durable clinical benefit observed using ICB depends on the immune status of tumors, notably the presence of cytotoxic effector immune cells. In our paper, we revealed that genetically targeting the autophagy-related protein PIK3C3/VPS34 in melanoma and colorectal tumor cells, or treating tumor-bearing mice with selective inhibitors of the PIK3C3/VPS34 kinase activity, reprograms cold immune desert tumors into hot, inflamed immune infiltrated tumors. Such reprograming results from the establishment of a proinflammatory signature characterized by the release of CCL5 and CXCL10 in the tumor microenvironment, and the subsequent recruitment of natural killer (NK) and CD8(+)T cells into the tumor bed. Furthermore, we reported that combining pharmacological inhibitors of PIK3C3/VPS34 improves the therapeutic benefit of anti-PD-1/PD-L1 immunotherapy. Our results provided the proof-of-concept to set-up innovative clinical trials for cold ICB-unresponsive tumors by combining PIK3C3/VPS34 inhibitors with anti-PDCD1/PD-1 and anti-CD274/PD-L1.
英文关键词	Autophagy cancer immunotherapy cold hot tumors colorectal cancer immune checkpoints immune infiltration melanoma NK and T CD8 cells proinflammatory cytokines VPS34
类型	Article
语种	英语
开放获取类型	Green Published, hybrid
收录类别	SCI-E
WOS记录号	WOS:000567020700001
WOS类目	Cell Biology
WOS研究方向	Cell Biology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/326114
作者单位	[Janji, Bassam; Hasmim, Meriem; Berchem, Guy; Noman, Muhammad Zaeem] Luxembourg Inst Hlth LIH, Tumor Immunotherapy & Microenvironm TIME Grp, Dept Oncol, Luxembourg, Luxembourg; [Parpal, Santiago; De Milito, Angelo] Sprint Biosci, Stockholm, Sweden; [Parpal, Santiago; De Milito, Angelo] Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden; [Berchem, Guy] Ctr Hosp Luxembourg, Dept Hematooncol, Luxembourg, Luxembourg
推荐引用方式 GB/T 7714	Janji, Bassam,Hasmim, Meriem,Parpal, Santiago,et al. Lighting up the fire in cold tumors to improve cancer immunotherapy by blocking the activity of the autophagy-related protein PIK3C3/VPS34[J],2020,16(11):2110-2111.
APA	Janji, Bassam,Hasmim, Meriem,Parpal, Santiago,De Milito, Angelo,Berchem, Guy,&Noman, Muhammad Zaeem.(2020).Lighting up the fire in cold tumors to improve cancer immunotherapy by blocking the activity of the autophagy-related protein PIK3C3/VPS34.AUTOPHAGY,16(11),2110-2111.
MLA	Janji, Bassam,et al."Lighting up the fire in cold tumors to improve cancer immunotherapy by blocking the activity of the autophagy-related protein PIK3C3/VPS34".AUTOPHAGY 16.11(2020):2110-2111.