GRIK2 is a target for bladder cancer stem-like cell-targeting immunotherapy
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ABSTRACT:
PROVIDER: PRJNA702454 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13731681.fastq.gz | Fastqsanger.gz | |||
| SRR13731682.fastq.gz | Fastqsanger.gz | |||
| SRR13731683.fastq.gz | Fastqsanger.gz | |||
| SRR13731684.fastq.gz | Fastqsanger.gz | |||
| SRR13731685.fastq.gz | Fastqsanger.gz |
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Project description:Recent studies revealed that treatment resistant cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be targeted by cytotoxic T lymphocytes (CTLs). CTLs recognize antigenic peptide derived from tumor-associated antigens (TAAs), thus identification of tumor-associated antigens (TAAs) expressed in CSCs/CICs is essential. Human leucocyte antigen (HLA) ligandome analysis using mass spectrometry enables analysis of naturally expressed antigenic peptides; however, HLA ligandome analysis requires large scale of sample and it is challenging for CSCs/CICs. In this study, we established novel bladder CSC/CIC model from a bladder cancer cell line UM-UC-3 cells using ALDEFLUOR assay. CSCs/CICs were isolated as aldehyde dehydrogenase (ALDH) high cells and several ALDHhigh clone cells were established. ALDHhigh clone cells were enriched with CSCs/CICs by sphere formation and tumorigenicity in immune deficient mouse. HLA ligandome analysis and gene expression (CAGE) using ALDHhigh clone cells revealed distinctive antigenic peptide repertoire in bladder CSCs/CICs, and we identified GRIK2 derived antigenic peptide is specifically expressed in CSCs/CICs. GRIK2 peptide-specific CTL clone recognized GRIK2-overexpressed UM-UC-3 cells and ALDHhigh clone cells indicating that GRIK2 peptide can be a novel target for bladder CSCs/CICs-targeting immunotherapy.
2021-10-01 | GSE166947 | GEO
Project description:Bladder cancer is a highly metastatic tumor and one of the most common malignant tumors originating in the urinary system. Although the application of immune checkpoint, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), achieved definite efficacy, the effect of immunotherapy for bladder cancer is still not very satisfactory. Therefore, it is very urgent to develop new targets to expand the options of immunotherapies. In this study, we utilized single cell sequencing to explore the cell composition and detected a subset of Treg cells with high expression of T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and interleukin (IL)-32 molecules. Certainly, anti-tumor immune response was suppressed by this subset of Treg cells and IL-32 promoted the bladder cancer metastasis. Nevertheless, targeting TIGIT not only could reverse immunosuppression through restoring anti-tumor immune response mediated by T cells but suppressed the secretion of IL-32 and inhibited the metastasis of bladder cancer cells. Thus, our study provided a novel insight into the immunosuppression in bladder cancer and developed the TIGIT as the novel target for immunotherapy of bladder cancer. Furthermore, we also illustrated mechanism of the dual effect of targeting TIGIT in bladder cancer and revealed the metastasis-promoting effect of IL-32 in bladder cancer. Taken together, the discovery raises the possibility of TIGIT targets against bladder cancer from the bench to the bedside.
2022-01-31 | GSE186520 | GEO
Project description:Abstract Background The global incidence of tumors is rising sharply. Immune checkpoint inhibitors (ICIs) represent the mainstream of immunotherapeutic approaches. Despite the remarkable clinical benefits of immunotherapy in various tumors, ICIs resistance remains an urgent challenge to be addressed. The transcription factors cAMP response element-binding protein 1(CREB1) and c-Jun converge to regulate oncogenesis and immune modulation. Methods Based on the 'CREBP1CJUN_01' gene set from the Molecular Signatures Database and single-cell RNA sequencing data, we identified 116 CREB–c-Jun transcription factor target-related differential genes (CR.Sig) and refined to 20 CREB–c-Jun transcription factor target-related important feature genes (Hub-CR.Sig) through multi-algorithm machine learning. These Hub-CR.Sig enabled prognostic risk modeling, molecular subtyping of bladder cancer, and somatic mutation stratification. Results Among these 20 signatures, RAD51C emerged as a top-ranked driver that was correlated with advanced T/N/M stages, associated with poor survival outcomes and is highly expressed in bladder cancer tissues. Functional assessment revealed that RAD51C knockdown suppressed bladder cancer cell proliferation, invasion, migration, and DNA repair capacity in vitro, while also reducing tumor formation in vivo. RNA sequencing analysis implicated the enrichment of JAK-STAT signaling pathways. Meanwhile, we identified an additional type of RAD51C+ fibroblast that was significantly associated with the depth of tumor invasion. Conclusions The study establishes the Hub-CR.Sig as an immunotherapy response classifier and nominates RAD51C targeting as a promising therapeutic strategy for bladder cancer.
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| S-EPMC10992913 | biostudies-literature
Project description:Full title: Predictive Gene Signatures as Strong Prognostic Indicators of the Effectiveness of Bacillus Calmetteâ??Guérin (BCG) Immunotherapy in Primary pT1 Bladder Cancers Intravesical BCG immunotherapy is effective in prevention of recurrence and progression in many cases of non-muscle invasive bladder cancer, but many patients fail to respond. This study identified predictive gene signatures in primary pT1 bladder cancer with BCG immunotherapy. Fourty-Eight patients with primary pT1 bladder cancer treated with BCG immunotherapy were used. Microarray gene expression analysis of the 48 primary bladder cancers was carried out. Predictive gene signatures were individually selected based on the recurrence and progression status. Among 43,148 unique genes, 424 and 287 candidate predictive genes that could predict recurrence and progression, respectively, were selected. Time to recurrence or progression was shorter for patients with poor-predictive gene signatures than good-predictive gene signatures (log-rank test, p <0.001, respectively). Validation of predictive gene signatures with RT-PCR was nearly identical to those of microarray (log-rank test, p <0.05, respectively). In multivariate regression analysis, predictive gene signatures were the only independent predictors of recurrence (HR 3.38, p = 0.048) or progression (HR 10.49, p = 0.048) in validation cohorts. Predictive gene signatures have strong diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer. Keywords: Gene expression, Bladder cancer, BCG Total RNA, extracted from the fresh frozen tissues of 48 pT1 bladder cancers, was isolated by TRIzol reagent (Life Technologies, NY, USA), according to the manufacturer's protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Five-hundred nanograms of total RNA were used for labeling hybridization according to the manufacturerâ??s protocol (Illumina HumanWG-6 BeadChip, version 2, Illumina, Inc., San Diego, CA, USA). Arrays were scanned with an Illumina Bead Array Reader confocal scanner (BeadStation 500GXDW; Illumina, Inc.) according to the manufacturer's instructions. Initial microarray gene expression data were obtained using Bead Studio software with gene expression analysis module (version 3.1.3, Illumina, Inc.).
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Project description:<p>The human immune system has evolved to interact with various commensal and pathogenic bacteria in intricate and nuanced ways. While the diversity of bacteria presents fundamental challenges in understanding immune-microbe interactions, it also offers ample opportunities for developing effective immunomodulatory therapies. We introduce microbial product cocktails as a novel class of immunotherapy for cancer. Using freshly resected tumors from bladder cancer patients, an immuno-comparative analysis of recruitment and enhancement assay, and an AI-guided optimization workflow, we established a personalized platform for identifying potent MPCs that promote recruitment, infiltration, and activation of immune cells for cancer treatment. In an orthotopic mouse bladder cancer model, MPCs demonstrated immunoenhancement and improved survival rates compared with standard bacillus Calmette–Guérin immunotherapy.</p>
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| PRJNA1057916 | ENA