Turning up the heat on non-immunoreactive tumors: pyroptosis influences the tumor immune microenvironment in bladder cancer

Chen, Xingyu; Chen, Haotian; Yao, Hong; Zhao, Kai; Zhang, Yao; He, Dong; Zhu, Yuxing; Cheng, Ying; Li, Rui; Xu, Runshi; Cao, Ke

doi:10.1038/s41388-021-02024-9

Cited by 63 publications

(60 citation statements)

References 34 publications

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“…Based on molecular characteristics, B7H4-high tumors could be defined as “cold” tumors, PDL1-high tumors were “hot” tumors, and co-low tumors were somewhere in between. Generally, patients with “hot” tumors exhibited a better prognosis and higher therapeutic response [ 17 – 19 ]. However, this assumption was not supported by survival analysis.…”

Section: Resultsmentioning

confidence: 99%

The B7H4-PDL1 classifier stratifies immuno-phenotype in cervical cancer

et al. 2022

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Background It has been revealed that B7H4 is negatively correlated with PDL1 and identifies immuno-cold tumors in glioma. However, the application of the B7H4-PDL1 classifier in cancers has not been well testified. Methods A pan-cancer analysis was conducted to evaluate the immunological role of B7H4 using the RNA-sequencing data downloaded from the Cancer Genome Atlas (TCGA). Immunohistochemistry (IHC) and multiplexed quantitative immunofluorescence (QIF) were performed to validate the primary results revealed by bioinformatics analysis. Results The pan-cancer analysis revealed that B7H4 was negatively correlated with PDL1 expression and immune cell infiltration in CeCa. In addition, patients with high B7H4 exhibited the shortest overall survival (OS) and relapse-free survival (RFS) while those with high PDL1 exhibited a better prognosis. Multiplexed QIF showed that B7H4 was mutually exclusive with PDL1 expression and the B7H4-high group exhibited the lowest CD8 + T cell infiltration. Besides, B7H4-high predicted highly proliferative subtypes, which expressed the highest Ki67 antigen. Moreover, B7H4-high also indicated a lower response to multiple therapies. Conclusions Totally, the B7H4-PDL1 classifier identifies the immunogenicity and predicts proliferative subtypes and limited therapeutic options in CeCa, which may be a convenient and feasible biomarker in clinical practice.

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Section: Resultsmentioning

confidence: 99%

The B7H4-PDL1 classifier stratifies immuno-phenotype in cervical cancer

et al. 2022

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“…Pyroptosis is a kind of cell necrosis that is triggered by the gasdermin protein family. Studies have shown that cytotoxic lymphocytes depend on pyroptosis to kill tumor cells, which are associated with the occurrence, development, and prognosis of bladder cancer [ 3 ]. In bladder cancer, the susceptibility of tumor cells to treatment is strongly linked with pyroptotic activity.…”

Section: Introductionmentioning

confidence: 99%

Prognosis Risk Model Based on Pyroptosis-Related lncRNAs for Bladder Cancer

Tang

et al. 2022

Disease Markers

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Objective. Bladder cancer (BC) is the most common malignancy in the urinary system and is prone to recurrence and metastasis. Pyroptosis is a kind of cell necrosis that is triggered by the gasdermin protein family. lncRNAs are noncoding RNAs that are more than 200 nucleotides long. Both pyroptosis and lncRNAs are associated with tumor development and progression. This study is aimed at exploring and establishing a prognostic signature of BC based on pyroptosis-related lncRNAs. Methods. In this study, The Cancer Genome Atlas (TCGA) database provided us with the RNA sequencing transcriptome data of bladder cancer patients, and we identified differentially expressed pyroptosis-related lncRNAs in bladder cancer. Then, the prognostic significance of these lncRNAs was assessed using univariate Cox regression analysis and LASSO regression analysis. Subsequently, 4 pyroptosis-related lncRNAs, namely, AL121652.1, AL161729.4, AC007128.1, and AC124312.3, were identified by multivariate Cox regression analysis, thus constructing the prognostic risk model. Then, we compared the levels of immune infiltration, differences in cell function, immune checkpoints, and m6A-related gene expression levels between the high- and low-risk groups. Result. Patients were divided into low-risk or high-risk groups based on the median risk score. Kaplan–Meier survival analysis indicated that the overall survival of bladder cancer patients in the low-risk group was substantially superior to that in the high-risk group ( p < 0.001 ). The receiver operating characteristic (ROC) curve further confirmed the credibility of our model. Moreover, gene set enrichment analysis (GSEA) indicated that these were different signal pathways significantly enriched between the two groups. Immune infiltration, immune checkpoint, and N6-methyladenosine-related gene analysis also reflected that there were notable differences between the two groups. Conclusion. Therefore, this prognostic risk model is based on the level of pyroptotic lncRNAs, which is conducive to individualized assessment of the risk of patients and provides a reference for clinical treatment. This will also help provide insights into the prognosis and treatment of bladder cancer.

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“…Pyroptosis is proven to be highly related to immune response, and recent evidence also reported the immunostimulatory function of pyroptosis, as well as a significant role in promoting the efficacy of cancer immunotherapy ( 23 , 24 ). The roles of some lncRNAs in cancer immunotherapy are also well-elucidated by various studies ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Role of a Pyroptosis-Related lncRNA Signature in Risk Stratification and Immunotherapy of Ovarian Cancer

Zhang

Yan

2022

Front. Med.

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Background: Pyroptosis is a newly recognized form of cell death. Emerging evidence has suggested the crucial role of long non-coding RNAs (lncRNAs) in the tumorigenesis and progression of ovarian cancer (OC). However, there is still poor understanding of pyroptosis-related lncRNAs in OC.Methods: The TCGA database was accessed for gene expression and clinical data of 377 patients with OC. Two cohorts for training and validation were established by random allocation. Correlation analysis and Cox regression analysis were performed to identify pyroptosis-related lncRNAs and construct a risk model.Results: Six pyroptosis-related lncRNAs were included in the final signature with unfavorable survival data. Subsequent ROC curves showed promising predictive value of patient prognosis. Further multivariate regression analyses confirmed the signature as an independent risk factor in the training (HR: 2.242, 95% CI: 1.598–3.145) and validation (HR: 1.884, 95% CI: 1.204–2.95) cohorts. A signature-based nomogram was also established with a C-index of.684 (95% CI: 0.662–0.705). Involvement of the identified signature in multiple immune-related pathways was revealed by functional analysis. Moreover, the signature was also associated with higher expression of three immune checkpoints (PD-1, B7-H3, and VSIR), suggesting the potential of the signature as an indicator for OC immunotherapies.Conclusion: This study suggests that the identified pyroptosis-related lncRNA signature and signature-based nomogram may serve as methods for risk stratification of OC. The signature is also associated with the tumor immune microenvironment, potentially providing an indicator for patient selection of immunotherapy in OC.

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Turning up the heat on non-immunoreactive tumors: pyroptosis influences the tumor immune microenvironment in bladder cancer

Cited by 63 publications

References 34 publications

The B7H4-PDL1 classifier stratifies immuno-phenotype in cervical cancer

The B7H4-PDL1 classifier stratifies immuno-phenotype in cervical cancer

Prognosis Risk Model Based on Pyroptosis-Related lncRNAs for Bladder Cancer

Role of a Pyroptosis-Related lncRNA Signature in Risk Stratification and Immunotherapy of Ovarian Cancer

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