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Stem and immune cell signatures indicate roles in invasion and metastasis, while regulatory T cells, dysplastic plasma cells, and early-stage macrophages suggest an immunosuppressive state. Neutrophils at cancer margins mirror inflammation, and enhanced autophagy in endothelial cells and fibroblasts implies nutrient supply. 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[https://doi.org/10.1038/s42003-024-05765-x](https://doi.org/10.1038/s42003-024-05765-x)  OPEN  \nSingle-cell transcriptomic analyses of tumor microenvironment and molecular reprograming landscape of metastatic laryngeal squamous cell carcinoma  \nYuanyuan Sun  1, Sheng Chen2, Yongping Lu3, Zhenming Xu  4✉, Weineng Fu  1 ✉ & Wei Yan  5,6✉  \nLaryngeal squamous cell carcinoma (LSCC) is a malignant tumor with a high probability of metastasis. The tumor microenvironment (TME) plays a critical role in cancer metastasis. To gain insights into the TME of LSCC, we conducted single-cell RNA-seq (scRNA-seq) on samples collected from LSCC patients with or without lymphatic metastasis. The stem and immune cell signatures in LSCC suggest their roles in tumor invasion and metastasis. Infiltration of a large number of regulatory T cells, dysplastic plasma cells, and macrophages that are at the early development stage in the cancerous tissue indicates an immunosuppressivestate. Abundant neutrophils detected at the cancer margins reflect the inflammatory microenvironment. In addition to dynamic ligand-receptor interactions between the stromaland myeloid cells, the enhanced autophagy in endothelial cells and fibroblasts implies a role in nutrient supply. Taken together, the comprehensive atlas of LSCC obtained allowed us to identify a complex yet unique TME of LSCC, which may help identify potential diagnostic biomarkers and therapeutic targets for LSCC.  \n1 Department of Medical Genetics, China Medical University, Shenyang 110122, China. 2 Department of Laboratory Animal Science, China Medical University, Shenyang 110122, China. 3 NHC Key Laboratory of Reproductive Health and Medical Genetics, Shenyang 110122, China. 4 Department of Otolaryngology, the Fourth People’s Hospital of Shenyang City, Shenyang 110031, China. 5 The Lundquist Institute for Biomedical Innovation at HarborUCLA Medical Center, Torrance, CA 90502, USA. 6 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.  \n✉ email: [zhenmingxu@cmu.edu.cn](zhenmingxu@cmu.edu.cn); [wnfu@cmu.edu.cn](wnfu@cmu.edu.cn); [wei.yan@lundquist.org](wei.yan@lundquist.org)  \nCOMMUNICATIONS BIOLOGY | (2024)7:63 | [https://doi.org/10.1038/s42003-024-05765-x|www.nature.com/commsbio](https://doi.org/10.1038/s42003-024-05765-x|www.nature.com/commsbio) 1  \nLaryngeal squamous cell carcinoma (LSCC) is one of the  \ncommon malignant tumors of the head and neck. The early  \nsymptoms of LSCC are not obvious and consequently, more than half of the patients, upon diagnosis, are already at the mid or late stage of tumor progression with infiltration and lymphatic metastasis 1. Recurrence and metastasis are two important factors affecting the five-year survival rate in LSCC patients2,3. Therefore, early diagnosis and prevention of metastasis are key to the treatment of LSCC. Since the concept of the tumor microenvironment (TME) emerged, it has been widely acknowledged that TME plays a critical role in tumor progression. The TME refers to a complex, heterogeneous composition of infiltrating immune and resident host cells, secreted factors, and extracellular matrix. Dynamic and reciprocal interactions between cancer cells and components of the TME lead to conditions that favor cancer cell survival, local invasion, and metastatic dissemination. For example, the TME can promote angiogenesis to overcome the hypoxic and acidic microenvironment; diverse adaptive and innate immune cells infiltrate the tumor to exert either pro- or anti-tumorigenic functions. Therefore, it is of great significance to study tumor-specific TME as it helps us not only understand tumor progression but also identify novel targets for diagnosticsand therapeutics. Indeed, TME-based precision medicine has drawn great attention over the last decade. In particular, personalized immunotherapies for lung cancer, ovarian cancer, and pancreatic cancer have widely been used in clinical practice, and consequently, the","cbCaicxHoj8dK9Ol","https://ap.wps.com/l/cbCaicxHoj8dK9Ol","pdf",6185899,15,"English","# Introduction\n## Study objectives and approach\n# Results\n## Single-cell atlas and cellular heterogeneity in metastatic LSCC","[{\"question\":\"What role does the tumor microenvironment (TME) play in LSCC metastasis?\",\"answer\":\"The TME critically influences cancer metastasis through interactions among immune and host cells, secreted factors, and extracellular matrix, which can promote survival, invasion, and metastatic dissemination.\"},{\"question\":\"How was the LSCC TME investigated in this study?\",\"answer\":\"Single-cell RNA-seq was performed on LSCC patient samples with lymphatic metastasis using the 10X Genomics platform, followed by detailed bioinformatic analyses to build a single-cell atlas.\"},{\"question\":\"Which cellular findings support immune suppression and inflammation in metastatic LSCC?\",\"answer\":\"Infiltration of regulatory T cells, dysplastic plasma cells, and early-stage macrophages indicates an immunosuppressive state, while abundant neutrophils at cancer margins reflect an inflammatory microenvironment.\"}]","Single-cell transcriptomic analyses of tumor microenvironment and molecular reprograming landscape of metastatic laryngeal squamous cell carcinoma - read and open access article summary | PDF",1789975061,38]