Comprehensive Characterization of Pyroptosis Phenotypes with Distinct Tumor Immune Profiles in Gastric Cancer to Aid Immunotherapy

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2023 Aug 18

PMID 37595258

Authors

Kaida Huang

Yubiao Lin

Guoqin Qiu

Shengyu Wang

Lihua Feng

Zhigao Zheng

Yingqin Gao

Xin Fan

Wenhui Zheng

Jianmin Zhuang

Fanghong Luo

Shuitu Feng

Affiliations

Soon will be listed here.

Abstract

Objective: Pyroptosis is a form of programmed cell death that is essential for immunity. Herein, this study was conducted to uncover the implication of pyroptosis in immunomodulation and tumor microenvironment (TME) in gastric cancer.

Methods: Prognostic pyroptosis-related genes were extracted to identify different pyroptosis phenotypes and pyroptosis genomic phenotypes via unsupervised clustering analysis in the gastric cancer meta-cohort cohort (GSE15459, GSE62254, GSE84437, GSE26253 and TCGA-STAD). The activation of hallmark gene sets was quantified by GSVA and immune cell infiltration was estimated via ssGSEA and CIBERSORT. Through PCA algorithm, pyroptosis score was conducted. The predictors of immune response (TMB and IPS) and genetic mutations were evaluated. The efficacy of pyroptosis score in predicting immune response was verified in two anti-PD-1 therapy cohorts.

Results: Three different pyroptosis phenotypes with different prognosis, biological pathways and tumor immune microenvironment were established among 1275 gastric cancer patients, corresponding to three immune phenotypes: immune-inflamed, immune-desert, and immune-excluded. According to the pyroptosis score, patients were separated into high and low pyroptosis score groups. Low pyroptosis score indicated favorable survival outcomes, enhanced immune responses, and increased mutation frequency. Moreover, low pyroptosis score patients displayed more clinical benefits from anti-PD-1 and prolonged survival time.

Conclusion: Our findings uncovered a nonnegligible role of pyroptosis in immunomodulation and TME multiformity and complicacy in gastric cancer. Quantifying the pyroptosis score in individual tumors may tailor more effective immunotherapeutic strategies.

Citing Articles

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Huang S, Huang L, Jiang Q, Jiang C, Guo G Clin Transl Oncol. 2024; .

PMID: 39690336 DOI: 10.1007/s12094-024-03832-7.

Research progress on the effect of pyroptosis on the occurrence, development, invasion and metastasis of colorectal cancer.

Wang X, Yin Q, Wan L, Sun R, Wang G, Gu J World J Gastrointest Oncol. 2024; 16(8):3410-3427.

PMID: 39171180 PMC: 11334039. DOI: 10.4251/wjgo.v16.i8.3410.

Application of pyroptosis score in the treatment and prognosis evaluation of gastric cancer.

Li L, Liao A Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024; 48(12):1882-1889.

PMID: 38448382 PMC: 10930744. DOI: 10.11817/j.issn.1672-7347.2023.230258.

References

Leek J, Johnson W, Parker H, Jaffe A, Storey J . The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28(6):882-3. PMC: 3307112. DOI: 10.1093/bioinformatics/bts034. View

Zhu X, Chen L, Liu L, Niu X . EMT-Mediated Acquired EGFR-TKI Resistance in NSCLC: Mechanisms and Strategies. Front Oncol. 2019; 9:1044. PMC: 6798878. DOI: 10.3389/fonc.2019.01044. View

Rosenberg J, Hoffman-Censits J, Powles T, van der Heijden M, Balar A, Necchi A . Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016; 387(10031):1909-20. PMC: 5480242. DOI: 10.1016/S0140-6736(16)00561-4. View

Wang X, Cheng G, Miao Y, Qiu F, Bai L, Gao Z . Piezo type mechanosensitive ion channel component 1 facilitates gastric cancer omentum metastasis. J Cell Mol Med. 2021; 25(4):2238-2253. PMC: 7882944. DOI: 10.1111/jcmm.16217. View

Segal B, Giridharan T, Suzuki S, Khan A, Zsiros E, Emmons T . Neutrophil interactions with T cells, platelets, endothelial cells, and of course tumor cells. Immunol Rev. 2022; 314(1):13-35. PMC: 10174640. DOI: 10.1111/imr.13178. View

Wu M, Wang Y, Yang D, Gong Y, Rao F, Liu R . A PLK1 kinase inhibitor enhances the chemosensitivity of cisplatin by inducing pyroptosis in oesophageal squamous cell carcinoma. EBioMedicine. 2019; 41:244-255. PMC: 6442225. DOI: 10.1016/j.ebiom.2019.02.012. View

Zeng Q, Yang F, Li C, Xu L, He X, Mai F . Paclitaxel Enhances the Innate Immunity by Promoting NLRP3 Inflammasome Activation in Macrophages. Front Immunol. 2019; 10:72. PMC: 6361797. DOI: 10.3389/fimmu.2019.00072. View

Geeleher P, Cox N, Huang R . pRRophetic: an R package for prediction of clinical chemotherapeutic response from tumor gene expression levels. PLoS One. 2014; 9(9):e107468. PMC: 4167990. DOI: 10.1371/journal.pone.0107468. View

Rosenbaum S, Wilski N, Aplin A . Fueling the Fire: Inflammatory Forms of Cell Death and Implications for Cancer Immunotherapy. Cancer Discov. 2021; 11(2):266-281. PMC: 7858229. DOI: 10.1158/2159-8290.CD-20-0805. View

10.

Zeng D, Li M, Zhou R, Zhang J, Sun H, Shi M . Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures. Cancer Immunol Res. 2019; 7(5):737-750. DOI: 10.1158/2326-6066.CIR-18-0436. View

11.

Qiu X, Song Y, Liu J, Wang Z, Niu X, He J . Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer. World J Gastrointest Oncol. 2020; 12(8):857-876. PMC: 7443845. DOI: 10.4251/wjgo.v12.i8.857. View

12.

Bousso P . Diving into the mechanism of action of tumor immunotherapies with intravital imaging. Immunol Rev. 2021; 306(1):218-223. DOI: 10.1111/imr.13032. View

13.

Alptekin A, Parvin M, Chowdhury H, Rashid M, Arbab A . Engineered exosomes for studies in tumor immunology. Immunol Rev. 2022; 312(1):76-102. PMC: 11044177. DOI: 10.1111/imr.13107. View

14.

Mariathasan S, Turley S, Nickles D, Castiglioni A, Yuen K, Wang Y . TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693):544-548. PMC: 6028240. DOI: 10.1038/nature25501. View

15.

Gambardella V, Castillo J, Tarazona N, Gimeno-Valiente F, Martinez-Ciarpaglini C, Cabeza-Segura M . The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target. Cancer Treat Rev. 2020; 86:102015. DOI: 10.1016/j.ctrv.2020.102015. View

16.

Li C, Qiu J, Xue Y . Low-dose Diosbulbin-B (DB) activates tumor-intrinsic PD-L1/NLRP3 signaling pathway mediated pyroptotic cell death to increase cisplatin-sensitivity in gastric cancer (GC). Cell Biosci. 2021; 11(1):38. PMC: 7881658. DOI: 10.1186/s13578-021-00548-x. View

17.

Kong X, Fu M, Niu X, Jiang H . Comprehensive Analysis of the Expression, Relationship to Immune Infiltration and Prognosis of TIM-1 in Cancer. Front Oncol. 2020; 10:1086. PMC: 7498659. DOI: 10.3389/fonc.2020.01086. View

18.

Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J . Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006; 98(4):262-72. DOI: 10.1093/jnci/djj052. View

19.

Neel D, Basu H, Gunner G, Chiu I . Catching a killer: Mechanisms of programmed cell death and immune activation in Amyotrophic Lateral Sclerosis. Immunol Rev. 2022; 311(1):130-150. PMC: 9489610. DOI: 10.1111/imr.13083. View

20.

Wilkerson M, Hayes D . ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics. 2010; 26(12):1572-3. PMC: 2881355. DOI: 10.1093/bioinformatics/btq170. View