Pyroptosis predicts immunotherapy outcomes across multiple cancer types

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2022-12, Vol.245, p.109163-109163, Article 109163
• Main Authors: Li, Song, Chen, Pengxiang, Cheng, Bo, Liu, Yuchen, Zhang, Xue, Xu, Qian, Huang, Miao, Dai, Xin, Huang, Kai, Zhang, Lin, Cheng, Yufeng, Liu, Lian
• Format: Article
• Language: English
• Subjects: Biomarker; Humans; Immune checkpoints; Immunotherapy; Neoplasms - drug therapy; Pyroptosis; Tumor Microenvironment
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2022.109163

Pyroptosis is a programmed cell death characterized by inflammation and may coordinate with cancer immunotherapy, but assessments of pyroptosis in patients with immunotherapy are lacking. We evaluated the pyroptosis potentials in 71 cohorts with 24,388 cancer patients. They were elevated in tumors compared to normal tissues but had a weak relationship with prognosis. High pyroptosis potentials indicated “hot tumors” characteristics and high objective response rates to PD1/PDL1 inhibitors derived from clinical trials. In 15 cohorts with patients treated with immunotherapy, a pyroptosis score showed predictive values in objective response rate, progression-free survival, and overall survival. Systematic treatments, such as chemotherapy or endocrine therapy, enhanced pyroptosis in drug-resistant tumors. These results were further validated in three independent clinical cohorts and our two institutional cohorts by immunohistochemistry. Our findings uncover a value of pyroptosis potentials to predict immunotherapy responses and a theoretical rationale for combining pyroptosis inducers and immunotherapy in cancer treatment. •There is a high pyroptosis level in tumors compared to normal tissues.•High pyroptosis potentials indicate characteristics of “hot tumors” in pan-cancer datasets.•Pyroptosis levels are associated with immunotherapy responses across multiple cancers.•Chemotherapy and endocrine therapy enhance pyroptosis in drug-resistant tumors.•The predicting roles of pyroptosis level are validated by immunohistochemistry staining.