PD-L1 controls cancer pyroptosis

Blasco, Maria; Gomis, Roger R.

doi:10.1038/s41556-020-00582-w

Cited by 18 publications

(14 citation statements)

References 14 publications

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“…Hou et al 70 found that antibiotic chemotherapy drugs could promote the combined effect of STAT3 and PD‐L1 to upregulate gasdermin C (GSDMC) under hypoxic conditions. It is worth noting that caspase‐8 can activate caspase‐3 to induce GSDMC‐mediated pyroptosis in breast cancer cells, 71 while STAT1 may also be associated with PD‐L1. Interestingly, it was also found that GSDMD and GSDME could directly induce pyroptosis, and that this mechanism is regarded as a significant biomarker that can predict the response to anti‐PD‐1 antibodies.…”

Section: Specific Relationship Between Pyroptosis and Immune Checkpointsmentioning

confidence: 99%

Pyroptosis, a new bridge to tumor immunity

et al. 2021

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Environmental factors and genetic mutation have caused cancer incidence and mortality to rapidly increase. Cancer has become one of the crucial causes of death worldwide, and is becoming a major public health problem. 1 The traditional core types of cancer treatment are surgery, chemo-therapy, and radiation therapy, which can reduce tumor cell proliferation by inducing cancer cell death. 2 However, accumulating evidence has shown that tumors often relapse and it has been suggested that successful oncotherapy requires prolonged antineoplastic immunity. 3 The field of cancer immunotherapy (CIT) has emerged in recent years and aims to stimulate the body's immune system to create a robust immune response that can kill cancer cells. 4 This type of treatment can induce immunogenic cell death in different ways and achieve long-term anticancer immunity. 5 Although the application of CIT has been considered for a broad range of tumors, only a minority of patients achieve a satisfactory treatment effect due to immune escape. These results indicate that the immune system is intricate and still not well managed. 6 Thus, it is necessary to explore the mechanisms involved in CIT to develop more efficient methods of treatment for better cancer prevention and treatment.

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Section: Specific Relationship Between Pyroptosis and Immune Checkpointsmentioning

confidence: 99%

Pyroptosis, a new bridge to tumor immunity

et al. 2021

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“…The efficiency of anti-PD-1 or PD-L1 therapy can be improved under pyroptosis-induced inflammation in the tumor microenvironment by chemotherapy, radiotherapy, and other therapeutic regimens ( Bergsbaken et al, 2009 ; Reck et al, 2019 ). Published clinical trials have shown that antibiotic chemotherapeutics can promote the combination of STAT3 and PD-L1 to upregulate GSDMC mediated pyroptosis under hypoxia ( Blasco and Gomis, 2020 ), which may improve HCC patient survival compared to patients received only a single type of treatment to improve the efficiency of PD-L1 inhibitors. TIGIT, similar to LAG3, belongs to the immunoglobulin superfamily and is exclusively expressed on lymphocytes, including CD8 + T cells, memory, and regulatory CD4 + T cells, follicular CD4 + T cells, and NK cells ( Stanietsky et al, 2009 ; Ge et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

The Pyroptosis-Related Gene Signature Predicts the Prognosis of Hepatocellular Carcinoma

Zhang

et al. 2022

Front. Mol. Biosci.

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Objective: Hepatocellular carcinoma (HCC) is a genetically and phenotypically heterogeneous tumor, and the prediction of its prognosis remains a challenge. In the past decade, studies elucidating the mechanisms that induce tumor cell pyroptosis has rapidly increased. The elucidation of their mechanisms is essential for the clinical development optimal application of anti-hepatocellular carcinoma therapeutics.Methods: Based on the different expression profiles of pyroptosis-related genes in HCC, we constructed a LASSO Cox regression pyroptosis-related genes signature that could more accurately predict the prognosis of HCC patients.Results: We identified seven pyroptosis-related genes signature (BAK1, CHMP4B, GSDMC, NLRP6, NOD2, PLCG1, SCAF11) in predicting the prognosis of HCC patients. Kaplan Meier survival analysis showed that the pyroptosis-related high-risk gene signature was associated with poor prognosis HCC patients. Moreover, the pyroptosis-related genes signature performed well in the survival analysis and ICGC validation group. The hybrid nomogram and calibration curve further demonstrated their feasibility and accuracy for predicting the prognosis of HCC patients. Meanwhile, the evaluation revealed that our novel signature predicted the prognosis of HCC patients more accurately than traditional clinicopathological features. GSEA analysis further revealed the novel signature associated mechanisms of immunity response in high-risk groups. Moreover, analysis of immune cell subsets with relevant functions revealed significant differences in aDCs, APC co-stimulation, CCR, check-point, iDCs, Macrophages, MHC class-I, Treg, and type II INF response between high- and low-risk groups. Finally, the expression of Immune checkpoints was enhanced in high-risk group, and m6A-related modifications were expressed differently between low- and high-risk groups.Conclusion: The novel pyroptosis-related genes signature can predict the prognosis of patients with HCC and insight into new cell death targeted therapies.

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“…Pyroptosis can enhance antitumor immunity for its immunogenic nature 37 . Recently research demonstrates pyroptosis of tumor cells may overcome tumor cells’ apoptosis resistance and promotes antitumor immunity 38 , 39 . However, the specific mechanism of tumors pyroptosis remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

LINC00511/hsa-miR-573 axis-mediated high expression of Gasdermin C associates with dismal prognosis and tumor immune infiltration of breast cancer

Sun

Chen

et al. 2022

Sci Rep

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Breast cancer (BC) is considered the second commonest human carcinoma and the most incident and mortal in the female population. Despite promising treatments for breast cancer, mortality rates of metastatic disease remain high. Gasdermin C (GSDMC) is an affiliate of the gasdermin (GSDM) family, which is involved in the process of pyroptosis. Pyroptosis is implicated in tumorigenesis, but the role of GSDMC in cancer cells is yet to be fully elucidated. In this study, we investigated the role and mechanism of GSDMC in breast cancer. We conducted a pan-cancer analysis of the expression and prognosis of GSDMC utilizing multidimensional data from The Cancer Genome Atlas (TCGA). We investigated GSDMC expression levels in 15 BC tissues and matched adjacent normal tissues by immunohistochemistry (IHC). Further verification was performed in the Gene Expression Omnibus (GEO) database. We discovered that elevated GSDMC expression was considerably linked to a worse prognosis in breast invasive carcinoma (BRCA). Next, we identified noncoding RNAs (ncRNAs) which contributing to higher expression of GSDMC by a series of expression, survival, and correlation analysis. We finally identified LINC00511/hsa-miR-573 axis to be the most promising ncRNA-associated pathways that account for GSDMC in BRCA. Furthermore, we demonstrated the significant correlations between GSDMC expression and immune infiltrates, immune checkpoints, and immune markers in BRCA. This study illustrated that ncRNAs-mediated upregulation of GSDMC linked to dismal prognosis and also exhibited a correlation with tumor immune cell infiltration in BRCA. It is anticipated to offer novel ideas for the link between pyroptosis and tumor immunotherapy.

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PD-L1 controls cancer pyroptosis

Cited by 18 publications

References 14 publications

Pyroptosis, a new bridge to tumor immunity

Pyroptosis, a new bridge to tumor immunity

The Pyroptosis-Related Gene Signature Predicts the Prognosis of Hepatocellular Carcinoma

LINC00511/hsa-miR-573 axis-mediated high expression of Gasdermin C associates with dismal prognosis and tumor immune infiltration of breast cancer

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