Journal Article

DKFZ-2024-02469

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy.

Yang, C. (First author)DKFZ* ; Geng, H. ; Yang, X. ; Ji, S. ; Liu, Z. ; Feng, H. ; Li, Q. ; Zhang, T. ; Zhang, S. ; Ma, X. ; Zhu, C. ; Xu, N. ; Xia, Y. ; Li, Y. ; Wang, H. ; Yu, C. ; Du, S.DKFZ* ; Miao, B.DKFZ* ; Xu, L. ; Wang, H. ; Cao, Y. ; Li, B. ; Zhu, L. ; Tang, X. ; Zhang, H. ; Zhu, C. ; Huang, Z. ; Leng, C. ; Hu, H. ; Chen, X. ; Yuan, S. ; Jin, G. ; Bernards, R. ; Sun, C.DKFZ* ; Zheng, Q. ; Qin, W. ; Gao, Q. ; Wang, C.

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.ccell.2024.10.008

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.

Keyword(s): CITE-seq ; hepatocellular carcinoma ; immunotherapy ; tumor-associated neutrophils ; tumor-initiating cells

Note: #EA:D250# /2024 Dec 9;42(12):2064-2081.e19

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Contributing Institute(s):

1. NWG Krebs-Immunregulation (D250)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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