Neglected, yet significant role of FOXP1 in T-cell quiescence, differentiation and exhaustion

Kaminskiy, Yaroslav; Kuznetsova, Varvara; Kudriaeva, Anna; Zmievskaya, Ekaterina; Bulatov, Emil

doi:10.3389/fimmu.2022.971045

Cited by 29 publications

(28 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10c). While the role of SOX4 in CD8+T cell development is unclear, FOXP1 has been shown to maintain a quiescent profile in naive CD8+T cells 88,89 , and our results are in keeping with a more activated profile in type 1 innate T cells. ARID5B has been reported to regulate metabolic programming and promote IFNγ production in NK cells 90 .…”

Section: Supplementary Notesupporting

confidence: 85%

Gene-level alignment of single cell trajectories

Sumanaweera¹,

Suo²,

Muraro³

et al. 2023

Preprint

View full text Add to dashboard Cite

Single cell data analysis can infer dynamic changes in cell populations, for example across time, space or in response to perturbation. To compare these dynamics between two conditions, trajectory alignment via dynamic programming (DP) optimization is frequently used, but is limited by assumptions such as a definite existence of a match. Here we describe Genes2Genes, a Bayesian information-theoretic DP framework for aligning single-cell trajectories. Genes2Genes overcomes current limitations and is able to capture sequential matches and mismatches between a reference and a query at single gene resolution, highlighting distinct clusters of genes with varying patterns of gene expression dynamics. Across both real life and simulated datasets, Genes2Genes accurately captured different alignment patterns, and revealed that T cells differentiated in vitro matched to an immature in vivo state while lacking the final TNFɑ signaling. This use case demonstrates that precise trajectory alignment can pinpoint divergence from the in vivo system, thus providing an opportunity to optimize in vitro culture conditions.

show abstract

Section: Supplementary Notesupporting

confidence: 85%

Gene-level alignment of single cell trajectories

Sumanaweera¹,

Suo²,

Muraro³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Loss of ACTRT1 function was reported to lead to aberrant activation of Hedgehog signalling in basal cell carcinoma 26 . Another example is Forkhead box protein 1 (FOXP1) on chromosome 3p13, which plays a role in T‐cell quiescence and differentiation 27 . Its deficiency has been reported to be correlated positively with tumour proliferation in prostate cancer or tumour origin in non‐small cell lung cancer 28 29 .…”

Section: Resultsmentioning

confidence: 99%

“…26 Another example is Forkhead box protein 1 (FOXP1) on chromosome 3p13, which plays a role in T-cell quiescence and differentiation. 27 Its deficiency has been reported to be correlated positively with tumour proliferation in prostate cancer or tumour origin in non-small cell lung cancer. 2829 These results suggest that HPV integration in the host genome may lead to the loss of function of genes that serve as tumour suppressors, thus accelerating tumourigenesis.…”

Section: Identification Of Integration Sites Co-occurred With Cnvsmentioning

confidence: 99%

Mapping the landscape of HPV integration and characterising virus and host genome interactions in HPV‐positive oropharyngeal squamous cell carcinoma

Xu,

Shi,

Zhou

et al. 2024

Clinical & Translational Med

View full text Add to dashboard Cite

BackgroundHuman papillomavirus (HPV) integration into the host genome is an important factor in HPV(+)OPSCC carcinogenesis, in conjunction with HPV oncoproteins E6/E7. However, a well‐studied investigation about virus–host interaction still needs to be completed. Our objective is to characterise HPV integration to investigate potential mechanisms of tumourigenesis independent of E6/E7 oncoproteins.Materials and methodsHigh‐throughput viral integration detection was performed on 109 HPV(+)OPSCC tumours with relevant clinicopathological information. Of these tumours, 38 tumours underwent targeted gene sequencing, 29 underwent whole exome sequencing and 26 underwent RNA sequencing.ResultsHPV integration was detected in 94% of tumours (with a mean integration count of 337). Tumours occurring at the tonsil/oropharyngeal wall that exhibit higher PD‐L1 expression demonstrated increased integration sites (p = .024). HPV exhibited a propensity for integration at genomic sites located within specific fragile sites (FRA19A) or genes associated with functional roles such as cell proliferation and differentiation (PTEN, AR), immune evasion (CD274) and glycoprotein biosynthesis process (FUT8). The viral oncogenes E2, E4, E6 and E7 tended to remain intact. HPV fragments displayed enrichment within host copy number variation (CNV) regions. However, insertions into genes related to altered homologous recombination repair were infrequent. Genes with integration had distinct expression levels. Fifty‐nine genes whose expression level was affected by viral integration were identified, for example, EPHB1, which was reported to be involved in cellular protein metabolic process.ConclusionsHPV can promote oncogenesis through recurrent integration into functional host genome regions, leading to subsequent genomic aberrations and gene expression disruption. This study characterises viral integrations and virus–host interactions, enhancing our understanding of HPV‐related carcinogenesis mechanisms.

show abstract

“…Furthermore, increasing evidence suggests that Treg cell infiltration in the TME is closely associated with poor prognosis and that the depletion of Treg cells may activate and enhance antitumor immune responses ( 42 ). Studies have revealed that Tregs play important roles in the microenvironment, prognosis, and chemotherapy response of various tumors ( 43 ). Shang et al.…”

Section: Discussionmentioning

confidence: 99%

Construction of a novel choline metabolism-related signature to predict prognosis, immune landscape, and chemotherapy response in colon adenocarcinoma

Liu

Wang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

BackgroundColon adenocarcinoma (COAD) is a common digestive system malignancy with high mortality and poor prognosis. Accumulating evidence indicates that choline metabolism is closely related to tumorigenesis and development. However, the efficacy of choline metabolism-related signature in predicting patient prognosis, immune microenvironment and chemotherapy response has not been fully clarified.MethodsCholine metabolism-related differentially expressed genes (DEGs) between normal and COAD tissues were screened using datasets from The Cancer Genome Atlas (TCGA), Kyoto Encyclopedia of Genes and Genomes (KEGG), AmiGO2 and Reactome Pathway databases. Two choline metabolism-related genes (CHKB and PEMT) were identified by univariate and multivariate Cox regression analyses. TCGA-COAD was the training cohort, and GSE17536 was the validation cohort. Patients in the high- and low-risk groups were distinguished according to the optimal cutoff value of the risk score. A nomogram was used to assess the prognostic accuracy of the choline metabolism-related signature. Calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were used to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and KEGG pathway enrichment analyses of DEGs in the high- and low-risk groups were performed. KEGG cluster analysis was conducted by the KOBAS-i database. The distribution and expression of CHKB and PEMT in various types of immune cells were analyzed based on single-cell RNA sequencing (scRNA-seq). The CIBERSORT and ESTIMATE algorithms evaluated tumor immune cell infiltration in the high- and low-risk groups. Evaluation of the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs based on the choline metabolism-related signature was performed. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking is used to simulate the binding conformation of small molecule compounds and key targets. By immunohistochemistry (IHC), Western blot, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiments, the expression levels of CHKB and PEMT in human, mouse, and cell lines were detected.ResultsWe constructed and validated a choline metabolism-related signature containing two genes (CHKB and PEMT). The overall survival (OS) of patients in the high-risk group was significantly worse than that of patients in the low-risk group. The nomogram could effectively and accurately predict the OS of COAD patients at 1, 3, and 5 years. The DCA curve and CIC demonstrate the clinical utility of the nomogram. scRNA-seq showed that CHKB was mainly distributed in endothelial cells, while PEMT was mainly distributed in CD4+ T cells and CD8+ T cells. In addition, multiple types of immune cells expressing CHKB and PEMT differed significantly. There were significant differences in the immune microenvironment, immune checkpoint expression and chemotherapy response between the two risk groups. In addition, we screened five potential small molecule drugs that targeted treatment for COAD. Finally, the results of IHC, Western blot, and qRT-PCR consistently showed that the expression of CHKB in human, mouse, and cell lines was elevated in normal samples, while PMET showed the opposite trend.ConclusionIn conclusion, we constructed a choline metabolism-related signature in COAD and revealed its potential application value in predicting the prognosis, immune microenvironment, and chemotherapy response of patients, which may lay an important theoretical basis for future personalized precision therapy.

show abstract

Neglected, yet significant role of FOXP1 in T-cell quiescence, differentiation and exhaustion

Cited by 29 publications

References 52 publications

Gene-level alignment of single cell trajectories

Gene-level alignment of single cell trajectories

Mapping the landscape of HPV integration and characterising virus and host genome interactions in HPV‐positive oropharyngeal squamous cell carcinoma

Construction of a novel choline metabolism-related signature to predict prognosis, immune landscape, and chemotherapy response in colon adenocarcinoma

Contact Info

Product

Resources

About