Single-cell transcriptome profiling of the stepwise progression of head and neck cancer

Choi, Ji-Hye; Lee, Bok‐Soon; Jang, Jeon Yeob; Lee, Yun Sang; Kim, Hyo Jeong; Roh, Jin; Shin, Yoo Seob; Woo, Hyun Goo; Kim, Chul‐Ho

doi:10.1038/s41467-023-36691-x

Cited by 58 publications

(58 citation statements)

References 41 publications

(46 reference statements)

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“…According to Figure 1B, TILs were highly prevalent among the cell types in the TME of chordoma. TILs have an impact on the advancement of tumours and their metastasis 10,29 . To further understand the heterogeneity of TILs in chordoma, we performed unsupervised clustering analysis on a population of 18 615 TILs.…”

Section: Resultsmentioning

confidence: 99%

“…Earlier investigations using single‐cell RNA sequencing (scRNA‐seq) have provided insights into the interactions between tumours and the immune system, uncovered a detailed network of ligands and receptors within chordomas and identified p‐epithelial–mesenchymal transition (EMT) as a crucial molecular target for chordoma treatment 7,8 . scRNA‐seq has offered an unparalleled understanding of intratumoural transcriptomic diversity in various cancers, highlighting the significance of specific cell populations in drug resistance and tumour prognosis 9,10 . However, there is still an incomplete understanding of the heterogeneity between primary and recurrent chordoma and the mechanisms underlying chordoma recurrence.…”

Section: Introductionmentioning

confidence: 99%

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Unravelling the role of immune cells and FN1 in the recurrence and therapeutic process of skull base chordoma

Huo,

Ma,

Wang

et al. 2023

Clinical & Translational Med

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BackgroundSkull base chordoma is a rare and aggressive tumour of the bone that has a high likelihood of recurrence. The fundamental differences in single cells between primary and recurrent lesions remain poorly understood, impeding development of effective treatment approaches.MethodsTo obtain an understanding of the differences in single cells between primary and recurrent chordomas, we performed single‐cell RNA sequencing and T‐cell/B‐cell receptor (BCR) sequencing. This allowed us to delineate the differences between the two types of tumour cells, tumour‐infiltrating lymphocytes, myeloid cells, fibroblasts and B cells. Copy number variants (CNVs) were detected and compared between the tumour types to assess heterogeneity. Selected samples were subjected to immunohistochemistry to validate protein expression. Fluorescence in situ hybridisation experiments, Transwell assays and xenograft mouse models helped verify the role of fibronectin 1 (FN1) in chordoma.ResultsPromoting natural killer (NK) cell and CD8_GZMK T‐cell function or inhibiting the transformation of CD8_GZMK T cells to CD8_ZNF683 T cells and promoting the transformation of natural killer T (NKT) cells to NK cells are promising strategies for preventing chordoma recurrence. Additionally, inhibiting the M2‐like activity of tumour‐associated macrophages (TAMs) could be an effective approach. Antigen‐presenting cancer‐associated fibroblasts (apCAFs) and dendritic cells (DCs) with high enrichment of the antigen‐presenting signature were enriched in primary chordomas. There were fewer plasma cells and BCR clonotypes in recurrent chordomas. Remarkably, FN1 was upregulated, had more CNVs, and was more highly secreted by tumours, macrophages, CD4 T cells, CD8 T cells and fibroblasts in recurrent chordoma than in primary chordoma. Finally, FN1 enhanced the invasion and proliferation of chordomas in vivo and in vitro.ConclusionOur comprehensive picture of the microenvironment of primary and recurrent chordomas provides deep insights into the mechanisms of chordoma recurrence. FN1 is an important target for chordoma therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unravelling the role of immune cells and FN1 in the recurrence and therapeutic process of skull base chordoma

Huo,

Ma,

Wang

et al. 2023

Clinical & Translational Med

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“…M1-like TAMs are recognized as being strongly related to favorable outcomes in patients with oral cancer . Therefore, we used single-cell RNA sequencing data obtained from the GEA database under accession code GSE181919 to investigate whether a substantial amount of macrophages had infiltrated into the microenvironment of OSCC. Compared with that in normal oral epithelial tissues and oral leukoplakia (LP), OSCC tissues exhibited significantly higher macrophage infiltration.…”

Section: Resultsmentioning

confidence: 99%

Ultrasound-Induced Gold Nanoparticle United with Acoustic Reprogramming of Macrophages for Enhanced Cancer Therapy

Tang,

Zhang,

Luo

et al. 2023

ACS Appl. Mater. Interfaces

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Sonodynamic therapy (SDT) has considerable potential in cancer treatment and exhibits high tissue penetration with minimal damage to healthy tissues. The efficiency of SDT is constrained by the complex immunological environment and tumor treatment resistance. Herein, a specific acoustic-actuated tumor-targeted nanomachine is proposed to generate mechanical damage to lysosomes for cancer SDT. The hybrid nanomachine was assembled with gold nanoparticles (GNPs) as the core and encapsulated with macrophage exosomes modified by AS1411 aptamers (GNP@EXO-APs) to optimize the pharmacokinetics and tumor aggregation. GNP@EXO-APs could be specifically transferred to the lysosomes of tumor cells. After induction with ultrasound, GNP@EXO-APs generated strong mechanical stress to produce lysosomal-dependent cell death in cancer cells. Notably, tumor-associated macrophages were reprogrammed in the ultrasound environment to an antitumor phenotype. Enhanced mechanical destruction via GNP@EXO-APs and immunotherapy of cancer cells were verified both in vitro and in vivo under SDT. This study provides a new direction for inside-out killing effects on tumor cells for cancer treatment.

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“…5 Several studies have been conducted from various perspectives to understand the molecular features of HNSCC depending on HPV status. [6][7][8][9][10] Because metastasis is a prominent cause of mortality in HNSCC, ongoing efforts aim to distinguish between the intertumoral and immunological properties of primary and metastatic sites. 11 However, despite the differences in metastasis patterns between HPV + and HPV − patients, only a few studies have specifically compared the tumor microenvironment (TME) between HPV + and HPV − HNSCC in the context of lymph node metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have been conducted from various perspectives to understand the molecular features of HNSCC depending on HPV status 6‐10 . Because metastasis is a prominent cause of mortality in HNSCC, ongoing efforts aim to distinguish between the intertumoral and immunological properties of primary and metastatic sites 11 .…”

Section: Introductionmentioning

confidence: 99%

Deciphering head and neck cancer microenvironment: Single‐cell and spatial transcriptomics reveals human papillomavirus‐associated differences

Lee,

Park,

Yun

et al. 2024

Journal of Medical Virology

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Human papillomavirus (HPV) is a major causative factor of head and neck squamous cell carcinoma (HNSCC), and the incidence of HPV‐associated HNSCC is increasing. The role of tumor microenvironment in viral infection and metastasis needs to be explored further. We studied the molecular characteristics of primary tumors (PTs) and lymph node metastatic tumors (LNMTs) by stratifying them based on their HPV status. Eight samples for single‐cell RNA profiling and six samples for spatial transcriptomics (ST), composed of matched primary tumors (PT) and lymph node metastases (LNMT), were collected from both HPV‐negative (HPV−) and HPV‐positive (HPV+) patients. Using the 10x Genomics Visium platform, integrative analyses with single‐cell RNA sequencing were performed. Intracellular and intercellular alterations were analyzed, and the findings were confirmed using experimental validation and publicly available data set. The HPV+ tissues were composed of a substantial amount of lymphoid cells regardless of the presence or absence of metastasis, whereas the HPV− tissue exhibited remarkable changes in the number of macrophages and plasma cells, particularly in the LNMT. From both single‐cell RNA and ST data set, we discovered a central gene, pyruvate kinase muscle isoform 1/2 (PKM2), which is closely associated with the stemness of cancer stem cell‐like populations in LNMT of HPV− tissue. The consistent expression was observed in HPV− HNSCC cell line and the knockdown of PKM2 weakened spheroid formation ability. Furthermore, we found an ectopic lymphoid structure morphology and clinical effects of the structure in ST slide of the HPV+ patients and verified their presence in tumor tissue using immunohistochemistry. Finally, the ephrin‐A (EPHA2) pathway was detected as important signals in angiogenesis for HPV− patients from single‐cell RNA and ST profiles, and knockdown of EPHA2 declined the cell migration. Our study described the distinct cellular composition and molecular alterations in primary and metastatic sites in HNSCC patients based on their HPV status. These results provide insights into HNSCC biology in the context of HPV infection and its potential clinical implications.

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Single-cell transcriptome profiling of the stepwise progression of head and neck cancer

Cited by 58 publications

References 41 publications

Unravelling the role of immune cells and FN1 in the recurrence and therapeutic process of skull base chordoma

Unravelling the role of immune cells and FN1 in the recurrence and therapeutic process of skull base chordoma

Ultrasound-Induced Gold Nanoparticle United with Acoustic Reprogramming of Macrophages for Enhanced Cancer Therapy

Deciphering head and neck cancer microenvironment: Single‐cell and spatial transcriptomics reveals human papillomavirus‐associated differences

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