TY  - JOUR
AU  - Yang, Chen
AU  - Geng, Haigang
AU  - Yang, Xupeng
AU  - Ji, Shuyi
AU  - Liu, Zhicheng
AU  - Feng, Hao
AU  - Li, Qian
AU  - Zhang, Tangansu
AU  - Zhang, Sisi
AU  - Ma, Xuhui
AU  - Zhu, Chuchen
AU  - Xu, Nuo
AU  - Xia, Yuhan
AU  - Li, Yan
AU  - Wang, Hongye
AU  - Yu, Chune
AU  - Du, Shangce
AU  - Miao, Beiping
AU  - Xu, Lei
AU  - Wang, Hui
AU  - Cao, Ying
AU  - Li, Botai
AU  - Zhu, Lili
AU  - Tang, Xiangyu
AU  - Zhang, Haoyu
AU  - Zhu, Chunchao
AU  - Huang, Zhao
AU  - Leng, Chao
AU  - Hu, Haiyan
AU  - Chen, Xiaoping
AU  - Yuan, Shengxian
AU  - Jin, Guangzhi
AU  - Bernards, René
AU  - Sun, Chong
AU  - Zheng, Quan
AU  - Qin, Wenxin
AU  - Gao, Qiang
AU  - Wang, Cun
TI  - Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy.
JO  - Cancer cell
VL  - 42
IS  - 12
SN  - 1535-6108
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-02469
SP  - 2064-2081.e19
PY  - 2024
N1  - #EA:D250# /2024 Dec 9;42(12):2064-2081.e19
AB  - 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.
KW  - CITE-seq (Other)
KW  - hepatocellular carcinoma (Other)
KW  - immunotherapy (Other)
KW  - tumor-associated neutrophils (Other)
KW  - tumor-initiating cells (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39515328
DO  - DOI:10.1016/j.ccell.2024.10.008
UR  - https://inrepo02.dkfz.de/record/294754
ER  -