A novel four‐gene signature predicts immunotherapy response of patients with different cancers

Liu, Yuanli; Ni, Mingyue; Li, Lamei; Wang, Junyan; Tu, Zhenzhen; Zhou, Haisheng; Zhang, Siping

doi:10.1002/jcla.24494

Cited by 4 publications

(2 citation statements)

References 61 publications

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“…Of note, a high level of STAT5A has already shown a correlation with resistance to epidrugs [67]. Additionally, high expression of RPS28, CTBP2, JAZF1, TCF7 and NECTIN1 and low expression of HERC5 and CTSH in the more sensitive models have previously been shown to influence drug sensitivity [68][69][70][71][72][73]. Of note, a low methylation level of JAZF1 has been correlated with a stronger effect of decitabine in endometriosis [71].…”

Section: Discussionmentioning

confidence: 95%

Pre-Clinical Evaluation of the Hypomethylating Agent Decitabine for the Treatment of T-Cell Lymphoblastic Lymphoma

Provez

Landfors

Roels

et al. 2023

Cancers

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T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10–20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing. Here, we targeted the recently described DNA hypermethylated profile in T-LBL with the DNA hypomethylating agent decitabine. We evaluated the anti-lymphoma properties and downstream effects of decitabine, using patient derived xenograft (PDX) models. Decitabine treatment resulted in prolonged lymphoma-free survival in all T-LBL PDX models, which was associated with downregulation of the oncogenic MYC pathway. However, some PDX models showed more benefit of decitabine treatment compared to others. In more sensitive models, differentially methylated CpG regions resulted in more differentially expressed genes in open chromatin regions. This resulted in stronger downregulation of cell cycle genes and upregulation of immune response activating transcripts. Finally, we suggest a gene signature for high decitabine sensitivity in T-LBL. Altogether, we here delivered pre-clinical proof of the potential use of decitabine as a new therapeutic agent in T-LBL.

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Section: Discussionmentioning

confidence: 95%

Pre-Clinical Evaluation of the Hypomethylating Agent Decitabine for the Treatment of T-Cell Lymphoblastic Lymphoma

Provez

Landfors

Roels

et al. 2023

Cancers

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“…CD8B , together with CD8A , code for integral glycoproteins on the surfaces of many immune cells and are co-receptors for antigen recognition by T cell receptors (TCRs) [ 106 ]. Moreover, CD8B was one of the biomarkers found to be present in more than 10% of the patients who developed an overt autoimmune response after SARS-CoV-2 infection and is one of the four-gene signature panel for a prognostic immune checkpoint blockade in different cancers [ 107 , 108 ]. This implicates a strong association between the CD8B gene and chronic immune diseases like IBD.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptomic and Targeted Genomic Profiling Adjusted for Inflammation and Therapy Bias Reveal CRTAM and PLCB1 as Novel Hub Genes for Anti-Tumor Necrosis Factor Alpha Therapy Response in Crohn’s Disease

Gorenjak,

Gole,

Goričan

et al. 2024

Pharmaceutics

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Background: The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn’s disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression signals, which may be masked due to the treatment or ongoing inflammation; Methods: The single-cell RNA sequencing was performed on PBMC samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells and an association analysis summary. Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds throughout the analyses. An additional assessment proved causal inference of both genes in response to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy or inflammation.

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