CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance

Cheng Wang; Yang Li; Lingfei Jia; Jin Koo Kim; Jiong Li; Peng Deng; Wuchang Zhang; Paul H Krebsbach; Cun-Yu Wang

doi:10.1016/j.stem.2021.04.011

CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance

Cell Stem Cell. 2021 Sep 2;28(9):1597-1613.e7. doi: 10.1016/j.stem.2021.04.011. Epub 2021 May 3.

Authors

Cheng Wang¹, Yang Li¹, Lingfei Jia¹, Jin Koo Kim², Jiong Li¹, Peng Deng¹, Wuchang Zhang¹, Paul H Krebsbach², Cun-Yu Wang³

Affiliations

¹ Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, Jonsson Comprehensive Cancer Center and Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Division of Constitutive and Regenerative Sciences, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, Jonsson Comprehensive Cancer Center and Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: cwang@dentistry.ucla.edu.

Abstract

Immunosurveillance is a critical mechanism guarding against tumor development and progression. Checkpoint inhibitors have shown significant success in cancer treatment, but expression of key factors such as PD-L1 in putative cancer stem cell (CSC) populations in squamous cell carcinoma has been inconclusive, suggesting that CSCs may have developed other mechanisms to escape immune surveillance. Here we show that CSCs upregulate the immune checkpoint molecule CD276 (B7-H3) to evade host immune responses. CD276 is highly expressed by CSCs in mouse and human head and neck squamous cell carcinoma (HNSCC) and can be used to prospectively isolate tumorigenic CSCs. Anti-CD276 antibodies eliminate CSCs in a CD8⁺ T cell-dependent manner, inhibiting tumor growth and lymph node metastases in a mouse HNSCC model. Single-cell RNA sequencing (RNA-seq) showed that CD276 blockade remodels SCC heterogeneity and reduces epithelial-mesenchymal transition. These results show that CSCs utilize CD276 for immune escape and suggest that targeting CD276 may reduce CSCs in HNSCC.

Keywords: BMI1; CD276; cancer stem cell; head and neck squamous cell carcinoma; immune surveillance; lineage tracing.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Carcinoma, Squamous Cell*
Cell Line, Tumor
Head and Neck Neoplasms*
Mice
Neoplastic Stem Cells
Squamous Cell Carcinoma of Head and Neck

Abstract

Publication types

MeSH terms

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