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Cancer Immunology Research
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Research Articles

Targeting CMTM6 Suppresses Stem Cell–Like Properties and Enhances Antitumor Immunity in Head and Neck Squamous Cell Carcinoma

Lei Chen, Qi-Chao Yang, Yi-Cun Li, Lei-Lei Yang, Jian-Feng Liu, Hao Li, Yao Xiao, Lin-Lin Bu, Wen-Feng Zhang and Zhi-Jun Sun
Lei Chen
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Qi-Chao Yang
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Yi-Cun Li
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Lei-Lei Yang
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Jian-Feng Liu
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Hao Li
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Yao Xiao
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Lin-Lin Bu
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Wen-Feng Zhang
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
2Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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Zhi-Jun Sun
1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
2Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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  • ORCID record for Zhi-Jun Sun
  • For correspondence: sunzj@whu.edu.cn
DOI: 10.1158/2326-6066.CIR-19-0394 Published February 2020
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Abstract

CMTM6, a regulator of PD-L1 expression, also modulates tumor immunity. Little is known about the function of CMTM6 and its mechanism of action in head and neck squamous cell carcinoma (HNSCC). In this study, we found by IHC analysis that CMTM6 overexpression predicted a poor prognosis for patients with HNSCC. We discovered that CMTM6 expression was correlated with increased activity through the Wnt/β-catenin signaling pathway, which is essential for tumorigenesis, maintenance of cancer stem cells (CSC), and the epithelial-to-mesenchymal transition (EMT) characteristic of multiple cancers. We used short hairpin RNA to eliminate expression of CMTM6, which led, in HNSCC cells, to reduced expression of nuclear β-catenin as well as inhibition of stem cell–like properties, TGFβ-induced EMT, and cell proliferation. Consistent with these results, we identified a significant positive correlation between expression of CMTM6 and EMT- and CSC-related genes in The Cancer Genome Atlas (TCGA). We found positive correlations for both RNA and protein between expression of CMTM6 and immune checkpoint components. CMTM6 silencing–induced PD-L1 downregulation delayed SCC7 tumor growth and increased CD8+ and CD4+ T-cell infiltration. The proportions of PD-1+, TIM-3+, VISTA+, LAG-3+, and B7-H3+ exhausted T cells were decreased significantly in the CMTM6 knockdown group. CMTM6 thus regulates stemness, EMT, and T-cell dysfunction and may be a promising therapeutic target in the treatment of HNSCC.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Cancer Immunol Res 2020;8:179–91

  • Received May 27, 2019.
  • Revision received October 14, 2019.
  • Accepted November 22, 2019.
  • Published first November 26, 2019.
  • ©2019 American Association for Cancer Research.
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Cancer Immunology Research: 8 (2)
February 2020
Volume 8, Issue 2
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Targeting CMTM6 Suppresses Stem Cell–Like Properties and Enhances Antitumor Immunity in Head and Neck Squamous Cell Carcinoma
Lei Chen, Qi-Chao Yang, Yi-Cun Li, Lei-Lei Yang, Jian-Feng Liu, Hao Li, Yao Xiao, Lin-Lin Bu, Wen-Feng Zhang and Zhi-Jun Sun
Cancer Immunol Res February 1 2020 (8) (2) 179-191; DOI: 10.1158/2326-6066.CIR-19-0394

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Targeting CMTM6 Suppresses Stem Cell–Like Properties and Enhances Antitumor Immunity in Head and Neck Squamous Cell Carcinoma
Lei Chen, Qi-Chao Yang, Yi-Cun Li, Lei-Lei Yang, Jian-Feng Liu, Hao Li, Yao Xiao, Lin-Lin Bu, Wen-Feng Zhang and Zhi-Jun Sun
Cancer Immunol Res February 1 2020 (8) (2) 179-191; DOI: 10.1158/2326-6066.CIR-19-0394
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