Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.
Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Southwest Medical University, Luzhou, Sichuan, China.
Front Immunol. 2022 Nov 14;13:1050951. doi: 10.3389/fimmu.2022.1050951. eCollection 2022.
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).
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.
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.
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.
癌症干细胞（CSC）被认为是导致头颈部鳞状细胞癌（HNSCC）多药耐药、转移、复发和免疫抑制的原因。然而，CSC 的异质性仍有待研究。在这项研究中，我们旨在确定 CSC 的异质性及其对肿瘤微环境（TME）形成的影响。
我们通过单细胞 RNA-seq 分析来自公共数据库的 20 个 HNSCC 组织，描绘了 HNSCC 转录组图谱，以揭示肿瘤内 CSC 的细胞成分、轨迹变化、信号网络、恶性状态和功能富集。
免疫检查点分子 CD276、LILRB2、CD47 在 CSC 中显著上调，使宿主抗肿瘤反应减弱或受损。值得注意的是，幼稚 CSC 被分为具有不同功能的 2 种不同类型的细胞，表现出功能多样性。此外，CSC 通过 WNT 和 ncWNT 信号进行自我更新和肿瘤转移活动。其中，调控因子（IRF1_394g、IRF7_160g、NFKB1_12g、NFKB2_33g 和 STAT1_356g）在亚组 2 和 3 中被激活，表明它们在肿瘤炎症反应过程中发挥关键作用。在所有 CSC 中，幼稚 CSC 似乎最恶性，导致预后更差。
我们的研究揭示了 CSC 在 HNSCC 进展过程中的主要信号转导和生物学功能，强调了 CSC 的异质性及其在免疫抑制性 TME 形成中的潜在机制。因此，我们关于 HNSCC 中 CSC 异质性的研究可为 HNSCC 的治疗提供新的见解。
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