Tbc1d10c is a selective, constitutive suppressor of the CD8 T-cell anti-tumor response

Cohen, Adrienne O.; Woo, Seung-Hyun; Zhang, Junya; Cho, Jiyoon; Ruiz, Marlon E.; Gong, Jonathan; Du, Rong; Yarygina, Olga; Jafri, Danya Z.; Bachelor, Michael; Finlayson, Michael O.; Soni, Rajesh Kumar; Hayden, Matthew S.; Owens, David M.

doi:10.1080/2162402x.2022.2141011

Cited by 4 publications

(5 citation statements)

References 74 publications

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“…Among the CTLG with cS/E = 10 or beyond and high expression (40 or beyond) ( Fig 5A ), GBP5 , PTPRC ( CD45 ), and TBC1D10C ( CARABIN ) were identified (red bars), among which prognostic difference of only TBC1D10C was statistically significant (p = 0.026) ( Fig 5C ). TBC1D10C knockout mice showed accumulated CTL like IGFBP3 [ 39 ]. We then explored group of genes with low cS/E for CTL activation indicators (red letters in S3 Table ), because CD8A is ascribed to the group ( Fig 2D ).…”

Section: Resultsmentioning

confidence: 99%

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CAF-associated genes putatively representing distinct prognosis by in silico landscape of stromal components of colon cancer

Okuno,

Ikemura,

Okamoto

et al. 2024

PLoS ONE

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Comprehensive understanding prognostic relevance of distinct tumor microenvironment (TME) remained elusive in colon cancer. In this study, we performed in silico analysis of the stromal components of primary colon cancer, with a focus on the markers of cancer-associated fibroblasts (CAF) and tumor-associated endothelia (TAE), as well as immunological infiltrates like tumor-associated myeloid cells (TAMC) and cytotoxic T lymphocytes (CTL). The relevant CAF-associated genes (CAFG)(representing R index = 0.9 or beyond with SPARC) were selected based on stroma specificity (cancer stroma/epithelia, cS/E = 10 or beyond) and expression amounts, which were largely exhibited negative prognostic impacts. CAFG were partially shared with TAE-associated genes (TAEG)(PLAT, ANXA1, and PTRF) and TAMC-associated genes (TAMCG)(NNMT), but not with CTL-associated genes (CTLG). Intriguingly, CAFG were prognostically subclassified in order of fibrosis (representing COL5A2, COL5A1, and COL12A1) followed by exclusive TAEG and TAMCG. Prognosis was independently stratified by CD8A, a CTL marker, in the context of low expression of the strongest negative prognostic CAFG, COL8A1. CTLG were comprehensively identified as IFNG, B2M, and TLR4, in the group of low S/E, representing good prognosis. Our current in silico analysis of the micro-dissected stromal gene signatures with prognostic relevance clarified comprehensive understanding of clinical features of the TME and provides deep insights of the landscape.

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Section: Resultsmentioning

confidence: 99%

“…TBC1D10C was statistically significant (p = 0.026) (Fig 5C). TBC1D10C knockout mice showed accumulated CTL like IGFBP3 [39]. We then explored group of genes with low cS/E for CTL activation indicators (red letters in S3 Table ), because CD8A is ascribed to the group (Fig 2D).…”

Section: Plos Onementioning

confidence: 99%

CAF-associated genes putatively representing distinct prognosis by in silico landscape of stromal components of colon cancer

Okuno,

Ikemura,

Okamoto

et al. 2024

PLoS ONE

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“…Co-expression studies have identified numerous genes with positive and negative correlations with S1PR4 ; the two genes with the strongest positive and negative correlations are TBC1D10C and ADGRA3 , respectively. TBC1D10C belongs to the EPI64 family and promotes tumor development by inhibiting T cell-mediated anti-tumor immunity [ 19 ]. TBC1D10C deficiency can increase the number and cytotoxic activity of CD8 + T cells without affecting CD4 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic role of sphingosine 1-phosphate receptor 4 (S1PR4) as a biomarker of skin cutaneous melanoma

Wang,

Pan,

Zhang

2024

Heliyon

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“…In addition, TMSB10 is closely associated with various tumor phenotypes such as cell proliferation, apoptosis, and angiogenesis ( 51 ), while overexpressed in HCC tissues and can affect distant tumor metastasis ( 52 ). TBC1D10C mediates Map3k3-NF-κB signaling axis activation to inhibit CD8 T cell activation and anti-tumor function thus promoting tumor progression ( 53 ). It is considered a tumor immunotherapy target ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

“…TBC1D10C mediates Map3k3-NF-κB signaling axis activation to inhibit CD8 T cell activation and anti-tumor function thus promoting tumor progression ( 53 ). It is considered a tumor immunotherapy target ( 53 ). In previous studies, CTSC was considered a key molecule in squamous cell carcinoma as well as breast cancer ( 54 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing

et al. 2023

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BackgroundHepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients.MethodsThe International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR.Result11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong.ConclusionTEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies.

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Tbc1d10c is a selective, constitutive suppressor of the CD8 T-cell anti-tumor response

Cited by 4 publications

References 74 publications

CAF-associated genes putatively representing distinct prognosis by in silico landscape of stromal components of colon cancer

CAF-associated genes putatively representing distinct prognosis by in silico landscape of stromal components of colon cancer

Expression and prognostic role of sphingosine 1-phosphate receptor 4 (S1PR4) as a biomarker of skin cutaneous melanoma

T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing

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