%0 Journal Article
%A Yang, Chen
%A Geng, Haigang
%A Yang, Xupeng
%A Ji, Shuyi
%A Liu, Zhicheng
%A Feng, Hao
%A Li, Qian
%A Zhang, Tangansu
%A Zhang, Sisi
%A Ma, Xuhui
%A Zhu, Chuchen
%A Xu, Nuo
%A Xia, Yuhan
%A Li, Yan
%A Wang, Hongye
%A Yu, Chune
%A Du, Shangce
%A Miao, Beiping
%A Xu, Lei
%A Wang, Hui
%A Cao, Ying
%A Li, Botai
%A Zhu, Lili
%A Tang, Xiangyu
%A Zhang, Haoyu
%A Zhu, Chunchao
%A Huang, Zhao
%A Leng, Chao
%A Hu, Haiyan
%A Chen, Xiaoping
%A Yuan, Shengxian
%A Jin, Guangzhi
%A Bernards, René
%A Sun, Chong
%A Zheng, Quan
%A Qin, Wenxin
%A Gao, Qiang
%A Wang, Cun
%T Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy.
%J Cancer cell
%V 42
%N 12
%@ 1535-6108
%C New York, NY
%I Elsevier
%M DKFZ-2024-02469
%P 2064-2081.e19
%D 2024
%Z #EA:D250# /2024 Dec 9;42(12):2064-2081.e19
%X Tumor-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.
%K CITE-seq (Other)
%K hepatocellular carcinoma (Other)
%K immunotherapy (Other)
%K tumor-associated neutrophils (Other)
%K tumor-initiating cells (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39515328
%R 10.1016/j.ccell.2024.10.008
%U https://inrepo02.dkfz.de/record/294754