Single-cell profiling of tumor-infiltrating TCF1/TCF7+ T cells reveals a T lymphocyte subset associated with tertiary lymphoid structures/organs and a superior prognosis in oral cancer

Peng, Yu; Xiao, Liping; Rong, Haixu; Ou, Zhanpeng; Cai, Tingting; Liu, Niu; Li, Bowen; Zhang, Lizao; Wu, Fan; Lan, Tian; Lin, Xinyu; Li, Qunxing; Ren, Siqi; Fan, ST; Li, Jinsong

doi:10.1016/j.oraloncology.2021.105348

Cited by 36 publications

(31 citation statements)

References 48 publications

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“…While it is not known what drives TLS formation, we observe differential expression of B cell chemokine CXCL13 and its receptor CXCR5 in OMAS tumors compared to non-OMAS ( Table S1 ), two features correlated strongly with ectopic lymphoid structure formation in a variety of settings in both cancer and autoimmunity (reviewed in Kazanietz et al 2019). A TCF7+ T cell subset has independently been identified as enriched in TLSs of an oral solid tumor, and predictive of positive tumor outcomes (Peng et al 2021). Consistent with both TLS enrichment and superior outcomes in OMAS associated tumors, TCF7 is strongly differentially expressed in OMAS tumors.…”

Section: Discussionmentioning

confidence: 99%

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

Rosenberg

Greenstein

Buchkovich

et al. 2021

Preprint

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Neuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop Opsoclonus Myoclonus Ataxia Syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem-directed autoimmunity, but typically with outstanding cancer-related outcomes. We compared tumor transcriptomes and tumor infiltrating T- and B-cell repertoires from 38 OMAS subjects with neuroblastoma to 26 non-OMAS associated neuroblastomas. We found greater B- and T-cell infiltration in OMAS-associated tumors compared to controls, but unexpectedly showed that both were polyclonal expansions. Tertiary lymphoid structures (TLS) were enriched in OMAS-associated tumors. We identified significant enrichment of the MHC Class II allele HLA-DOB*01:01 in OMAS patients. OMAS severity scores were associated with the expression of several candidate autoimmune genes. We propose a model in which polyclonal autoreactive B lymphocytes act as antigen presenting cells and drive TLS formation, thereby crucially supporting both sustained polyclonal T-cell-mediated anti-tumor immunity and paraneoplastic OMAS neuropathology.

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Section: Discussionmentioning

confidence: 99%

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

Rosenberg

Greenstein

Buchkovich

et al. 2021

Preprint

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“…ScRNA-Seq data from the GSE150321 ( Song et al, 2020 ) and GSE172577 ( Peng et al, 2021 ) datasets were obtained from the GEO database. The R packages “Seurat” (version 4.0.2) and “scCancer” ( Guo et al, 2021 ) were used to process the data.…”

Section: Methodsmentioning

confidence: 99%

Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma

Huang

Liang

Dong

et al. 2022

Front. Cell Dev. Biol.

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Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy of the mucosal epithelium of the oral cavity, pharynx, and larynx. Laryngeal squamous cell carcinoma (LSCC) and oral squamous cell carcinoma are common HNSCC subtypes. Patients with metastatic HNSCC have a poor prognosis. Therefore, identifying molecular markers for the development and progression of HNSCC is essential for improving early diagnosis and predicting patient outcomes.Methods: Gene expression RNA-Seq data and patient clinical traits were obtained from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) and Gene Expression Omnibus databases. Differentially expressed gene (DEG) screening was performed using the TCGA-HNSC dataset. Intersection analysis between the DEGs and a list of core matrisome genes obtained from the Matrisome Project was used to identify differentially expressed matrisome genes. A prognostic model was established using univariate and multivariate Cox regression analyses, least absolute shrinkage, and selection operator (LASSO) regression analysis. Immune landscape analysis was performed based on the single-sample gene set enrichment analysis algorithm, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, prognostic value, receiver operating characteristic curve analysis, and gene mutation analyses. Immunohistochemical results regarding prognostic protein levels were obtained from the Human Protein Atlas. Single-gene RNA-sequencing data were obtained from GSE150321 and GSE172577 datasets. CCK-8 and Transwell assays were used to confirm cell proliferation and migration.Results: A total of 1,779 DEGs, including 939 upregulated and 840 downregulated genes, between tumor and normal samples were identified using the TCGA-HNSC microarray data. Intersection analysis revealed 52 differentially expressed matrisome-related genes. After performing univariate and multivariate Cox regression and LASSO analyses, a novel prognostic model based on six matrisome genes (FN1, LAMB4, LAMB3, DMP1, CHAD, and MMRN1) for HNSCC was established. This risk model can successfully predict HNSCC survival. The high-risk group had worse prognoses and higher enrichment of pathways related to cancer development than the low-risk group. Silencing LAMB4 in HNSCC cell lines promoted cell proliferation and migration.Conclusion: This study provides a novel prognostic model for HNSCC. Thus, FN1, LAMB4, LAMB3, DMP1, CHAD, and MMRN1 may be the promising biomarkers for clinical practice.

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“…The high resolution of scRNAseq extracted a Transcription Factor 7 (TCF7+) subpopulation in OSCC. 83 The DEG analysis of scRNA-seq data indicated these cells expressed high levels of tertiary lymphoid structures (TLS)-related genes and low levels of immune checkpoint molecules such as CTLA4…”

Section: Salivary Glandmentioning

confidence: 99%

“…and Lymphocyte Activating 3 (LAG3), which was associated with good prognosis. 83 Immunosuppressive drugs have achieved certain clinical effects, but not all HNSCC patients are sensitive to them. For example, results of clinical trials indicated that the overall response rate to the programmed death protein 1 (PD-1)-targeted drug was under 20%.…”

Section: Salivary Glandmentioning

confidence: 99%

“…The scRNA‐seq makes for characterizing the T cell subpopulations of OSCC and their gene expression profiles, advancing the checkpoint immunotherapy in OSCC. The high resolution of scRNA‐seq extracted a Transcription Factor 7 (TCF7+) subpopulation in OSCC 83 . The DEG analysis of scRNA‐seq data indicated these cells expressed high levels of tertiary lymphoid structures (TLS)‐related genes and low levels of immune checkpoint molecules such as CTLA4 and Lymphocyte Activating 3 (LAG3), which was associated with good prognosis 83 .…”

Section: In‐depth Study Of Oral Diseases Using Scrna‐seqmentioning

confidence: 99%

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Single‐cell RNA sequencing in oral science: Current awareness and perspectives

Ding

Wang

et al. 2022

Cell Proliferation

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The emergence of single-cell RNA sequencing enables simultaneous sequencing of thousands of cells, making the analysis of cell population heterogeneity more efficient. In recent years, single-cell RNA sequencing has been used in the investigation of heterogeneous cell populations, cellular developmental trajectories, stochastic gene transcriptional kinetics, and gene regulatory networks, providing strong support in life science research. However, the application of single-cell RNA sequencing in the field of oral science has not been reviewed comprehensively yet. Therefore, this paper reviews the development and application of single-cell RNA sequencing in oral science, including fields of tissue development, teeth and jaws diseases, maxillofacial tumors, infections, etc., providing reference and prospects for using single-cell RNA sequencing in studying the oral diseases, tissue development, and regeneration. | INTRODUCTIONOn the analysis of mixed samples of thousands of cells, bulk RNA sequencing is prone to uncover gene expression by sequencing on average in the absence of the cellular transcriptome heterogeneity of individual cells. Traditional RNA sequencing can reveal information of dominant cell subpopulations, but the transcriptome characteristics of rare cell subpopulations cannot be shown because the results are † Authors contributing equally to this article.

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Single-cell profiling of tumor-infiltrating TCF1/TCF7+ T cells reveals a T lymphocyte subset associated with tertiary lymphoid structures/organs and a superior prognosis in oral cancer

Cited by 36 publications

References 48 publications

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma

Single‐cell RNA sequencing in oral science: Current awareness and perspectives

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