Prioritizing exhausted T cell marker genes highlights immune subtypes in pan-cancer

Zhang, Chunlong; Sheng, Qi; Zhang, Xue; Xu, Kang; Jin, Xiaoyan; Zhou, Weiwei; Zhang, Mingjie; Lv, Dezhong; Yang, Changbo; Li, Yongsheng; Xu, Juan; Li, Xia

doi:10.1016/j.isci.2023.106484

Cited by 3 publications

(1 citation statement)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Initially, we compared the expression of various immune checkpoints within high and low ADRM1 expression groups. We compared the expression profiles of immune cell marker genes, extracted from CellMarker 2.0 32 and the study by Zhang et al 33 , between the high and low ADRM1 expression groups. Then, a comparative analysis of the composition of infiltrated immune cells were compared between the low and high ADRM1 expression groups using the CIBERSORT algorithm.…”

Section: Methodsmentioning

confidence: 99%

Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer

Yu,

Wang,

Liu

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Adhesion-regulating molecule 1 (ADRM1) has been implicated in tumor development, yet its specific role in bladder cancer (BC) remains undefined. This study aimed to elucidate the function of ADRM1 in BC through a combination of bioinformatics analysis and immunohistochemical analysis (IHC). Utilizing R version 3.6.3 and relevant packages, we analyzed online database data. Validation was conducted through IHC data, approved by the Institutional Ethics Committee (Approval No. K20220830). In both paired and unpaired comparisons, ADRM1 expression was significantly elevated in BC tissues compared to adjacent tissues, as evidenced by the results of TCGA dataset and IHC data. Patients with high ADRM1 expression had statistically worse overall survival than those with low ADRM1 expression in TCGA dataset, GSE32548 dataset, GSE32894 dataset, and IHC data. Functional analysis unveiled enrichment in immune-related pathways, and a robust positive correlation emerged between ADRM1 expression and pivotal immune checkpoints, including CD274, PDCD1, and PDCD1LG2. In tumor microenvironment, samples with the high ADRM1 expression contained statistical higher proportion of CD8 + T cells and Macrophage infiltration. Meanwhile, these high ADRM1-expressing samples displayed elevated tumor mutation burden scores and stemness indices, implying potential benefits from immunotherapy. Patients with low ADRM1 expression were sensitive to cisplatin, docetaxel, vinblastine, mitomycin C, and methotrexate. According to the findings from bioinformatics and IHC analyses, ADRM1 demonstrates prognostic significance for BC patients and holds predictive potential for both immunotherapy and chemotherapy responses. This underscores its role as a biomarker and therapeutic target in BC.

show abstract

Section: Methodsmentioning

confidence: 99%

Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer

Yu,

Wang,

Liu

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

Dysfunctional tumor-infiltrating Vδ1 + T lymphocytes in microsatellite-stable colorectal cancer

Stary,

Pandey,

List

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Although γδ T cells are known to participate in immune dysregulation in solid tumors, their relevance to human microsatellite-stable (MSS) colorectal cancer (CRC) is still undefined. Here, using integrated gene expression analysis and T cell receptor sequencing, we characterized γδ T cells in MSS CRC, with a focus on Vδ1 + T cells. We identified Vδ1 + T cells with shared motifs in the third complementarity-determining region of the δ-chain, reflective of antigen recognition. Changes in gene and protein expression levels suggested a dysfunctional effector state of Vδ1 + T cells in MSS CRC, distinct from Vδ1 + T cells in microsatellite-instable (MSI). Interaction analysis highlighted an immunosuppressive role of fibroblasts in the dysregulation of Vδ1 + T cells in MSS CRC via the TIGIT-NECTIN2 axis. Blocking this pathway with a TIGIT antibody partially restored cytotoxicity of the dysfunctional Vδ1 phenotype. These results define an operative pathway in γδ T cells in MSS CRC.

show abstract

Simulating CD8 T Cell Exhaustion: A Comprehensive Approach

Manrique-Rincón,

Foster,

Horswell

et al. 2024

Preprint

View full text Add to dashboard Cite

Immunotherapy has revolutionised the treatment of multiple cancer types, however, these treatments only work for a proportion of patients and biomarkers to predict response are lacking. One correlate of response is the reinvigoration of a subset of CD8 T cells that have an exhausted phenotype and impaired functionality. In order to develop new therapies, reproducible models are required to identify candidate target genes that enables the reversal of key hallmarks of T cell exhaustion. Here we describe the development of anin vitromodel by chronically stimulating T cells with their cognate antigen and performed an in depth temporal phenotypic characterisation. This model recapitulates many of the critical hallmarks of exhaustion, including increased expression of canonical exhaustion surface markers, impaired proliferation, reduced cytokine production, decreased release of cytotoxic granules, and metabolic alterations, including dysfunctional mitochondria. These exhaustion hallmarks were validated using anin vivomodel and a gene signature identified which robustly define the sharedin vitroandin vivoexhausted state. Critically, this signature is also observed in tumour infiltrating T cells from multiple human tumour types, validating the translational potential of this model for discovering and triaging new therapies.

show abstract

Prioritizing exhausted T cell marker genes highlights immune subtypes in pan-cancer

Cited by 3 publications

References 81 publications

Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer

Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer

Dysfunctional tumor-infiltrating Vδ1 + T lymphocytes in microsatellite-stable colorectal cancer

Simulating CD8 T Cell Exhaustion: A Comprehensive Approach

Contact Info

Product

Resources

About