Single-cell RNA sequencing reveals TCR+ macrophages in HPV-related head and neck squamous cell carcinoma

Jiang, Yourong; Zhang, Siwei; Tang, Lu; Li, Rui; Zhai, Jinglei; Luo, Suisui; Peng, Yiman; Chen, Xiaohang; Wei, Lanlan

doi:10.3389/fimmu.2022.1030222

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…Cells expressing FABP5 , a marker for lipid‐rich foamy macrophages, 23 were enriched in C3, suggesting that they could be lipid‐laden foam macrophages. In concordance with a previous report 24 there was a distinct subcluster (C6) with enrichment of cells expressing the T cell marker gene ( CD3D ) and TCR marker genes TRAC (Figure 4A,E), suggesting that they could be CD3 + TCR + macrophage cell populations.…”

Section: Resultssupporting

confidence: 92%

Single‐cell transcriptomic analysis of gingivo‐buccal oral cancer reveals two dominant cellular programs

Kurkalang,

Roy,

Acharya

et al. 2023

Cancer Science

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Oral squamous cell carcinoma of the gingivo‐buccal region (OSCC‐GB) is the most common cancer among men in India, and is associated with poor prognosis and frequent recurrence. Cellular heterogeneity in OSCC‐GB was investigated by single‐cell RNA sequencing of tumors derived from the oral cavity of 12 OSCC‐GB patients, 3 of whom had concomitant presence of a precancerous lesion (oral submucous fibrosis [OSMF]). Unique malignant cell types, features, and phenotypic shifts in the stromal cell population were identified in oral tumors with associated submucous fibrosis. Expression levels of FOS, ATP1A, and DUSP1 provided robust discrimination between tumors with or without the concomitant presence of OSMF. Malignant cell populations shared between tumors with and without OSMF were enriched with the expression of partial epithelial–mesenchymal transition (pEMT) or fetal cell type signatures indicative of two dominant cellular programs in OSCC‐GB—pEMT and fetal cellular reprogramming. Malignant cells exhibiting fetal cellular and pEMT programs were enriched with the expression of immune‐related pathway genes known to be involved in antitumor immune response. In the tumor microenvironment, higher infiltration of immune cells than the stromal cells was observed. The T cell population was large in tumors and diverse subtypes of T cells with varying levels of infiltration were found. We also detected double‐negative PLCG2+ T cells and cells with intermediate M1–M2 macrophage polarization. Our findings shed light on unique aspects of cellular heterogeneity and cell states in OSCC‐GB.

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Section: Resultssupporting

confidence: 92%

Single‐cell transcriptomic analysis of gingivo‐buccal oral cancer reveals two dominant cellular programs

Kurkalang,

Roy,

Acharya

et al. 2023

Cancer Science

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“…These two clusters, especially macroC3, also had high expression of KRT19, which may be the reason for their radioresistance 39 . Interestingly, macroC4 had high expression of CD3D and CD3E, which can activate TCR signalling 40 . We found that the number of TCR clonotypes of macroC4 was reduced in recurrent chordomas (Figures 3E and S14).…”

Section: Resultsmentioning

confidence: 79%

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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“…Interestingly, this population of macrophages also has higher expression of OLR1 , a marker of myeloid-derived suppressor cells (MDSC) in other tumors [40]. Macrophages expressing T-cell marker genes have been previously found in inflammatory diseases and head and neck squamous cell carcinoma [41, 42], however, their role in the OS TME is unclear.…”

Section: Resultsmentioning

confidence: 99%

Immunosuppressive tumor microenvironment of osteosarcoma

Taylor,

Sheng,

et al. 2023

Preprint

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BackgroundOsteosarcoma (OS) is the most common malignant bone tumor in children. OS is characterized by a high degree of genomic instability, resulting in copy-number alterations and genomic rearrangements with no disease-defining recurrent mutations. Given the diverse genomic landscape of OS and the difficulty of identifying druggable therapeutic targets, use of immunotherapy techniques appears lucrative. However, clinical trials based on molecular characterization have failed to find new effective therapies, and outcomes have not improved over the last 40 years.Materials/MethodsWe performed single-cell RNA sequencing (scRNA-seq) using the 10x Genomics Chromium platform on six fresh tumor biopsy samples from pediatric OS patients. Raw data was processed using 10x CellRanger to produce transcript read counts for each cell. After filtering low-quality cells and doublet removal, counts were normalized using Seurat, and cells were integrated across samples with Harmony. Data was combined with a previously-published OS scRNA-seq cohort of six samples (GSE162454). Two additional OS samples were profiled using 10x Genomics Visium spatial transcriptomics for validation of discovered subtypes and to add spatial context.ResultsClustering identified 16 major cell types based on expression of canonical cell markers. Several immunosuppressive cell types were identified via subclustering of major cell types, including neutrophil myeloid-derived suppressor cells (MDSCs), regulatory and exhausted T-cells, and LAMP3+ dendritic cells. Markers for the cell types found in OS were identified for further validation using imaging techniques, including Visium spatial transcriptomics. We performed deconvolution using the scRNA-seq cell identities to examine colocalization of discovered cell types. Overall, the discovered clusters were common between patients, showing consistent cell type proportions.However, we found patient-specific differences in the frequency of some cell types, with one sample showing a higher proportion of T-cells along with increased presence of colocalized IFN-stimulated macrophages, and the other with a greater presence of neutrophils/MDSCs.ConclusionsUsing single-cell transcriptomics, we were able to discover the presence of multiple immunosuppressive cell subtypes of neutrophils, T-cells, and dendritic cells. Additionally, spatial transcriptomics revealed multiple similar clusters between samples, and common colocalization of the discovered cell types within those clusters. However, differences in T-cell presence and interferon induction may be indicative of patient-specific immunogenicity in osteosarcoma tumors.

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Single-cell RNA sequencing reveals TCR+ macrophages in HPV-related head and neck squamous cell carcinoma

Cited by 11 publications

References 29 publications

Single‐cell transcriptomic analysis of gingivo‐buccal oral cancer reveals two dominant cellular programs

Single‐cell transcriptomic analysis of gingivo‐buccal oral cancer reveals two dominant cellular programs

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

Immunosuppressive tumor microenvironment of osteosarcoma

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