scholarly journals Single cell transcriptome revealed tumor associated antigen (TAA) profile in lung adenocarcinoma (LUAD)

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Fang Lv ◽  
Xueying Wu ◽  
Jin Song ◽  
Pan Wang ◽  
Shucheng Ren ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
T Cells ◽  
Lung Adenocarcinoma ◽  
Single Cell ◽  
Cancer Vaccines ◽  
Therapeutic Response ◽  
Tumor Associated Antigen ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractIt has been suggested that the heterogeneity of TAAs in lung cancer may affect the therapeutic response and disease progression. Up to now, several tumor-associated antigen (TAA)-based cancer vaccines have been investigated in lung adenocarcinoma (LUAD); however, most of them have failed at the stage of clinical trials. The present study suggests that inter-tumoral heterogeneity of TAAs is large at single-cell resolution, while the communication between tumor cells and infiltrating T cells is closely related to the expression profile of TAAs.

scholarly journals Single-cell transcriptome analysis demonstrates inter-patient and intra-tumor heterogeneity in primary and metastatic lung adenocarcinoma

Aging ◽  
2020 ◽  
Vol 12 (21) ◽  
pp. 21559-21581
Author(s):  
Yafei Liu ◽  
Guanchao Ye ◽  
Lan Huang ◽  
Chunyang Zhang ◽  
Yinliang Sheng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Single Cell ◽  
Transcriptome Analysis ◽  
Tumor Heterogeneity ◽  
Metastatic Lung ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Linking the T cell receptor to the single cell transcriptome in antigen‐specific human T cells

2016 ◽  
Vol 94 (6) ◽  
pp. 604-611 ◽  
Author(s):  
Auda A Eltahla ◽  
Simone Rizzetto ◽  
Mehdi R Pirozyan ◽  
Brigid D Betz‐Stablein ◽  
Vanessa Venturi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Human T Cells ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

scholarly journals Single-cell transcriptome of in vivo SIV-infected rhesus macaque CD4 T cells

2019 ◽  
Vol 5 ◽  
pp. 22
Author(s):  
A. Tokarev ◽  
A. Geretz ◽  
P. Ehrenberg ◽  
M. Roederer ◽  
R. Thomas ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Rhesus Macaque ◽  
Cd4 T Cells ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

scholarly journals Single-cell transcriptome analysis reveals TOX as a promoting factor for T-cell exhaustion and a predictor for anti-PD1 responses in human cancer

2019 ◽  
Author(s):  
Kyungsoo Kim ◽  
Seyeon Park ◽  
Seong Yong Park ◽  
Gamin Kim ◽  
Su Myeong Park ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Human Melanoma ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Candidate Regulator

ABSTRACTBackgroundT cells exhibit heterogeneous functional states in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) can reinvigorate only the stem cell-like progenitor exhausted T cells, which suggests that inhibiting the exhaustion progress will improve the efficacy of immunotherapy. Thus, regulatory factors promoting T-cell exhaustion could serve as potential targets for delaying the process and improving ICI efficacy.MethodsWe analyzed the single-cell transcriptome data derived from human melanoma and non-small cell lung cancer (NSCLC) samples and classified the tumor-infiltrating (TI) CD8+ T-cell population based on PDCD1 (PD-1) levels, i.e. PDCD1-high and PDCD1-low cells. Additionally, we identified differentially expressed genes as candidate factors regulating intra-tumoral T-cell exhaustion. The co-expression of candidate genes with immune checkpoint (IC) molecules in the TI CD8+ T cells was confirmed by single-cell trajectory and flow-cytometry analyses. The loss-of-function effect of the candidate regulator was examined by a cell-based knockdown assay. The clinical effect of the candidate regulator was evaluated based on the overall survival and anti-PD-1 responses.ResultsWe retrieved many known factors for regulating T-cell exhaustion among the differentially expressed genes between PDCD1-high and PDCD1-low subsets of the TI CD8+ T cells in human melanoma and NSCLC. TOX was the only transcription factor (TF) predicted in both tumor types. TOX levels tend to increase as CD8+ T cells become more exhausted. Flow-cytometry analysis revealed a correlation between TOX expression and severity of intra-tumoral T-cell exhaustion. TOX knockdown in the human TI CD8+ T cells resulted in downregulation of PD-1, TIM-3, TIGIT, and CTLA-4, which suggests that TOX promotes intra-tumoral T-cell exhaustion by upregulating IC proteins in cancer. Finally, the TOX level in the TI T cells was found to be highly predictive of overall survival and anti-PD-1 efficacy in melanoma and NSCLC.ConclusionsWe predicted the regulatory factors involved in T-cell exhaustion using single-cell transcriptome profiles of human TI lymphocytes. TOX promoted intra-tumoral CD8+ T-cell exhaustion via upregulation of IC molecules. This suggested that TOX inhibition can potentially impede T-cell exhaustion and improve ICI efficacy. Additionally, TOX expression in the TI T cells can be used for patient stratification during anti-tumor treatments, including anti-PD-1 immunotherapy.

scholarly journals Single-cell transcriptome analysis of the immunosuppressive effect of differential expression of tumor PD-L1 on responding TCR-T cells

2020 ◽  
Author(s):  
Renpeng Ding ◽  
Shang Liu ◽  
Shanshan Wang ◽  
Huanyi Chen ◽  
Fei Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Gene Clusters ◽  
Cellular Assays ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractPD-L1 expression levels in tumors do not consistently predict cancer patients’ response to PD-(L)1 inhibitors. We therefore evaluated how tumor PD-L1 levels affect the anti-PD-(L)1 efficacy and T cell function. We used MART-1-specific TCR-T cells (TCR-TMART-1) stimulated with MART-127-35 peptide-loaded MEL-526 tumor cells with different proportions of them expressing PD-L1 to perform cellular assays and high-throughput single-cell RNA sequencing. Compared to control T cells, TCR-TMART-1 were more sensitive to exhaustion and secreted lower pro-inflammatory but higher anti-inflammatory cytokines with increasing proportions of PD-L1+ tumor cells. The colocalization of T cells and tumor cells in gene clusters correlated negatively with the proportion of PD-L1+ tumor cells and positively with immune cell cytotoxicity. Moreover, elevated proportion of PD-L1+ tumor cells increased PD-L1 expression and decreased PD-1 expression on T cells and enhanced T cell death. The expression of PD-1 and PD-L1 in T cells and macrophages also correlated positively with COVID-19 severity.

scholarly journals Single-cell transcriptome analysis of the heterogeneous effects of differential expression of tumor PD-L1 on responding TCR-T cells

Theranostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 4957-4974
Author(s):  
Renpeng Ding ◽  
Shang Liu ◽  
Shanshan Wang ◽  
Huanyi Chen ◽  
Fei Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Differential Expression ◽  
Transcriptome Analysis ◽  
Heterogeneous Effects ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

scholarly journals Landscape Of M6a RNA Methylation Regulators and Tumor Microenvironment Cell-Infiltration Characterization In Gastroesophageal Adenocarcinomas

2021 ◽  
Author(s):  
Duanrui Liu ◽  
Jingyu Zhu ◽  
Zongming Wang ◽  
Yusong Fang ◽  
Mingjie Yuan ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Rna Methylation ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background: RNA N6-methyladenosine (m6A) modification plays a nonnegligible role in shaping individual tumor microenvironment (TME) characterizations. However, the landscape and relationship of m6A modification and TME cell infiltration remain unknown in gastroesophageal adenocarcinomas (GEA). Methods: We systematically examined the TME of GEA focusing on the distinct m6A modification patterns from the public databases. Intrinsic patterns of m6A modification were evaluated for associations with clinicopathological characteristics, underlying biological pathways, tumor immune cell infiltration, oncological outcomes and treatment responses. We generated a single-cell transcriptome atlas of the GEA sample inhouse to validate the role of the m6A modification pattern on TME.Results: We identified and validated the landscape of m6A regulators and tumor-infiltrating immune cells in GEA. Then, two distinct m6A modification patterns of GEA (cluster1/2 subgroup) were defined, and we correlated two subgroups with TME cell-infiltrating characteristics. Cluster2 subgroup correlates with a poorer prognosis, down-regulated PD-1 expression, higher risk scores and distinct immune cell infiltration. Additionally, PPI and WGCNA network analysis were integrated to identify key module genes closely related to immune infiltration of GEA to find immunotherapy markers. And COL4A1 and COL5A2 in brown module were significantly correlated to the prognosis, PD-1/L1 and CTLA-4 expression of GEA patients. Interesting, low COL5A2 expression was linked to an enhanced response to anti-PD-1 immunotherapy. Finally, a prognostic risk score was constructed using three m6A regulator-associated signatures that represented an independent prognosis factor for GEA. The single-cell transcriptome atlas of GEA sample validated the role of m6A modification pattern on TME and revealed that three m6A regulators are highly expressed in CD4+ T cells, CD8+ T cells, Tregs and Macrophages.Conclusions: Our work revealed m6A RNA methylation regulators are a type of vital participant in the malignant progression and TME diversity of GEA. m6A modification patterns of COL5A2 may be the potential biomarker contributes to predicting the response to anti-PD-1 immunotherapy.

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