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@ARTICLE{Yang:294754,
author = {C. Yang$^*$ and H. Geng and X. Yang and S. Ji and Z. Liu
and H. Feng and Q. Li and T. Zhang and S. Zhang and X. Ma
and C. Zhu and N. Xu and Y. Xia and Y. Li and H. Wang and C.
Yu and S. Du$^*$ and B. Miao$^*$ and L. Xu and H. Wang and
Y. Cao and B. Li and L. Zhu and X. Tang and H. Zhang and C.
Zhu and Z. Huang and C. Leng and H. Hu and X. Chen and S.
Yuan and G. Jin and R. Bernards and C. Sun$^*$ and Q. Zheng
and W. Qin and Q. Gao and C. Wang},
title = {{T}argeting the immune privilege of tumor-initiating cells
to enhance cancer immunotherapy.},
journal = {Cancer cell},
volume = {42},
number = {12},
issn = {1535-6108},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2024-02469},
pages = {2064-2081.e19},
year = {2024},
note = {#EA:D250# /2024 Dec 9;42(12):2064-2081.e19},
abstract = {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.},
keywords = {CITE-seq (Other) / hepatocellular carcinoma (Other) /
immunotherapy (Other) / tumor-associated neutrophils (Other)
/ tumor-initiating cells (Other)},
cin = {D250},
ddc = {610},
cid = {I:(DE-He78)D250-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39515328},
doi = {10.1016/j.ccell.2024.10.008},
url = {https://inrepo02.dkfz.de/record/294754},
}