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000294754 0247_ $$2doi$$a10.1016/j.ccell.2024.10.008
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000294754 1001_ $$0P:(DE-He78)8b693edfb7c78bb156cc92812eec1c55$$aYang, Chen$$b0$$eFirst author
000294754 245__ $$aTargeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy.
000294754 260__ $$aNew York, NY$$bElsevier$$c2024
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000294754 500__ $$a#EA:D250# /2024 Dec 9;42(12):2064-2081.e19
000294754 520__ $$aTumor-initiating cells (TICs) possess the ability to evade anti-tumor immunity, potentially explaining many failures of cancer immunotherapy. Here, we identify CD49f as a prominent marker for discerning TICs in hepatocellular carcinoma (HCC), outperforming other commonly used TIC markers. CD49f-high TICs specifically recruit tumor-promoting neutrophils via the CXCL2-CXCR2 axis and create an immunosuppressive milieu in the tumor microenvironment (TME). Reciprocally, the neutrophils reprogram nearby tumor cells toward a TIC phenotype via secreting CCL4. These cells can evade CD8+ T cell-mediated killing through CCL4/STAT3-induced and CD49f-stabilized CD155 expression. Notably, while aberrant CD155 expression contributes to immune suppression, it also represents a TIC-specific vulnerability. We demonstrate that either CD155 deletion or antibody blockade significantly enhances sensitivity to anti-PD-1 therapy in preclinical HCC models. Our findings reveal a new mechanism of tumor immune evasion and provide a rationale for combining CD155 blockade with anti-PD-1/PD-L1 therapy in HCC.
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000294754 650_7 $$2Other$$aCITE-seq
000294754 650_7 $$2Other$$ahepatocellular carcinoma
000294754 650_7 $$2Other$$aimmunotherapy
000294754 650_7 $$2Other$$atumor-associated neutrophils
000294754 650_7 $$2Other$$atumor-initiating cells
000294754 7001_ $$aGeng, Haigang$$b1
000294754 7001_ $$aYang, Xupeng$$b2
000294754 7001_ $$aJi, Shuyi$$b3
000294754 7001_ $$aLiu, Zhicheng$$b4
000294754 7001_ $$aFeng, Hao$$b5
000294754 7001_ $$aLi, Qian$$b6
000294754 7001_ $$aZhang, Tangansu$$b7
000294754 7001_ $$aZhang, Sisi$$b8
000294754 7001_ $$aMa, Xuhui$$b9
000294754 7001_ $$aZhu, Chuchen$$b10
000294754 7001_ $$aXu, Nuo$$b11
000294754 7001_ $$aXia, Yuhan$$b12
000294754 7001_ $$aLi, Yan$$b13
000294754 7001_ $$aWang, Hongye$$b14
000294754 7001_ $$aYu, Chune$$b15
000294754 7001_ $$0P:(DE-He78)842f32f9066384840481c90552ab2cff$$aDu, Shangce$$b16$$udkfz
000294754 7001_ $$0P:(DE-He78)b5b786a7a28d851956ba90aa9451887a$$aMiao, Beiping$$b17$$udkfz
000294754 7001_ $$aXu, Lei$$b18
000294754 7001_ $$aWang, Hui$$b19
000294754 7001_ $$aCao, Ying$$b20
000294754 7001_ $$aLi, Botai$$b21
000294754 7001_ $$aZhu, Lili$$b22
000294754 7001_ $$aTang, Xiangyu$$b23
000294754 7001_ $$aZhang, Haoyu$$b24
000294754 7001_ $$aZhu, Chunchao$$b25
000294754 7001_ $$aHuang, Zhao$$b26
000294754 7001_ $$aLeng, Chao$$b27
000294754 7001_ $$aHu, Haiyan$$b28
000294754 7001_ $$aChen, Xiaoping$$b29
000294754 7001_ $$aYuan, Shengxian$$b30
000294754 7001_ $$aJin, Guangzhi$$b31
000294754 7001_ $$aBernards, René$$b32
000294754 7001_ $$0P:(DE-He78)ef40d75e5564c492ee57b4262fc016fe$$aSun, Chong$$b33$$udkfz
000294754 7001_ $$aZheng, Quan$$b34
000294754 7001_ $$aQin, Wenxin$$b35
000294754 7001_ $$aGao, Qiang$$b36
000294754 7001_ $$aWang, Cun$$b37
000294754 773__ $$0PERI:(DE-600)2074034-7$$a10.1016/j.ccell.2024.10.008$$gp. S1535610824003969$$n12$$p2064-2081.e19$$tCancer cell$$v42$$x1535-6108$$y2024
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