TY - JOUR
T1 - Complex interaction and heterogeneity among cancer stem cells in head and neck squamous cell carcinoma revealed by single-cell sequencing
AU - Xiao, Mintao
AU - Zhang, Xinyi
AU - Zhang, Duoli
AU - Deng, Shuai
AU - Zheng, Anfu
AU - Du, Fukuan
AU - Shen, Jing
AU - Yue, Lin
AU - Yi, Tao
AU - Xiao, Zhangang
AU - Zhao, Yueshui
N1 - This work was supported by National Natural Science Foundation of China (No. 81972643, No. 82172962), Sichuan Science and Technology Project (2021YJ0201), Luxian People’s Government and Southwest Medical University Scientific and Technological Achievements Transfer and Transformation Strategic Cooperation Project (2019LXXNYKD-07) and Science and Technology Program of Luzhou, China (No. 21CGZHPT0001).
Publisher Copyright:
© 2022 Xiao, Zhang, Zhang, Deng, Zheng, Du, Shen, Yue, Yi, Xiao and Zhao.
PY - 2022/11/14
Y1 - 2022/11/14
N2 - Background: Cancer stem cells (CSCs) have been characterized to be responsible for multidrug resistance, metastasis, recurrence, and immunosuppressive in head and neck squamous cell carcinoma (HNSCC). However, the diversity of CSCs remains to be investigated. In this study, we aimed to determine the heterogeneity of CSCs and its effect on the formation of tumor microenvironment (TME).Methods: We depicted the landscape of HNSCC transcriptome profile by single-cell RNA-sequencing analysis of 20 HNSCC tissues from public databases, to reveal the Cell components, trajectory changes, signaling network, malignancy status and functional enrichment of CSCs within tumors.Results: Immune checkpoint molecules CD276, LILRB2, CD47 were significantly upregulated in CSCs, enabling host antitumor response to be weakened or damaged. Notably, naive CSCs were divided to 2 different types of cells with different functions, exhibiting functional diversity. In addition, CSCs underwent self-renewal and tumor metastasis activity through WNT and ncWNT signaling. Among them, Regulon regulators (IRF1_394g, IRF7_160g, NFKB1_12g, NFKB2_33g and STAT1_356g) were activated in subgroups 2 and 3, suggesting their pivotal roles in the inflammatory response process in tumors. Among all CSCs, naive CSCs appear to be the most malignant resulting in a worse prognosis.Conclusions: Our study reveals the major signal transduction and biological function of CSCs during HNSCC progression, highlighting the heterogeneity of CSCs and their underlying mechanisms in the formation of an immunosuppressive TME. Therefore, our study about heterogeneity of CSCs in HNSCC can bring new insights for the treatment of HNSCC.
AB - Background: Cancer stem cells (CSCs) have been characterized to be responsible for multidrug resistance, metastasis, recurrence, and immunosuppressive in head and neck squamous cell carcinoma (HNSCC). However, the diversity of CSCs remains to be investigated. In this study, we aimed to determine the heterogeneity of CSCs and its effect on the formation of tumor microenvironment (TME).Methods: We depicted the landscape of HNSCC transcriptome profile by single-cell RNA-sequencing analysis of 20 HNSCC tissues from public databases, to reveal the Cell components, trajectory changes, signaling network, malignancy status and functional enrichment of CSCs within tumors.Results: Immune checkpoint molecules CD276, LILRB2, CD47 were significantly upregulated in CSCs, enabling host antitumor response to be weakened or damaged. Notably, naive CSCs were divided to 2 different types of cells with different functions, exhibiting functional diversity. In addition, CSCs underwent self-renewal and tumor metastasis activity through WNT and ncWNT signaling. Among them, Regulon regulators (IRF1_394g, IRF7_160g, NFKB1_12g, NFKB2_33g and STAT1_356g) were activated in subgroups 2 and 3, suggesting their pivotal roles in the inflammatory response process in tumors. Among all CSCs, naive CSCs appear to be the most malignant resulting in a worse prognosis.Conclusions: Our study reveals the major signal transduction and biological function of CSCs during HNSCC progression, highlighting the heterogeneity of CSCs and their underlying mechanisms in the formation of an immunosuppressive TME. Therefore, our study about heterogeneity of CSCs in HNSCC can bring new insights for the treatment of HNSCC.
KW - single-cell sequencing
KW - head and neck squamous cell carcinoma
KW - cancer stem cell
KW - WNT signaling pathway
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=85142720286&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.1050951
DO - 10.3389/fimmu.2022.1050951
M3 - Journal article
C2 - 36451812
AN - SCOPUS:85142720286
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1050951
ER -