Pyroptosis predicts immunotherapy outcomes across multiple cancer types

被引：11

作者：

Li, Song ^{[1
]}

Chen, Pengxiang ^{[2
]}

Cheng, Bo ^{[3
]}

Liu, Yuchen ^{[2
]}

Zhang, Xue ^{[1
]}

Xu, Qian ^{[1
]}

Huang, Miao ^{[1
]}

Dai, Xin ^{[1
,4
]}

Huang, Kai ^{[1
]}

Zhang, Lin ^{[2
]}

Cheng, Yufeng ^{[2
]}

Liu, Lian ^{[1
]}

机构：

[1] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Med Oncol, 107 Wenhuaxi Rd, Jinan 250012, Peoples R China

[2] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Radiat Oncol, 107 Wenhuaxi Rd, Jinan 250012, Peoples R China

[3] Shandong Univ, Shandong Canc Hosp, Cheeloo Coll Med, 107 Wenhuaxi Rd, Jinan 250012, Peoples R China

[4] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Dept Oncol, Jinan, Peoples R China

来源：

CLINICAL IMMUNOLOGY | 2022年 / 245卷

基金：

中国国家自然科学基金;

关键词：

Pyroptosis; Immunotherapy; Biomarker; Tumor microenvironment; Immune checkpoints; INDUCE PYROPTOSIS; GASDERMIN D; CELL-DEATH; CHEMOTHERAPY; NIVOLUMAB; CASPASES; CLEAVAGE;

D O I：

10.1016/j.clim.2022.109163

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Pyroptosis is a programmed cell death characterized by inflammation and may coordinate with cancer immu-notherapy, 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 co-horts 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.

引用

页数：13

共 54 条

[1] xCell: digitally portraying the tissue cellular heterogeneity landscape [J].

Aran, Dvir ;

Hu, Zicheng ;

Butte, Atul J. .

GENOME BIOLOGY, 2017, 18

[2] Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression [J].

Becht, Etienne ;

Giraldo, Nicolas A. ;

Lacroix, Laetitia ;

Buttard, Benedicte ;

Elarouci, Nabila ;

Petitprez, Florent ;

Selves, Janick ;

Laurent-Puig, Pierre ;

Sautes-Fridman, Catherine ;

Fridman, Wolf H. ;

de Reynies, Aurelien .

GENOME BIOLOGY, 2016, 17

[3] Association Between Immune-Related Adverse Events During Anti-PD-1 Therapy and Tumor Mutational Burden [J].

Bomze, David ;

Ali, Omar Hasan ;

Bate, Andrew ;

Flatz, Lukas .

JAMA ONCOLOGY, 2019, 5 (11) :1633-1635

[4] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].

Brahmer, Julie ;

Reckamp, Karen L. ;

Baas, Paul ;

Crino, Lucio ;

Eberhardt, Wilfried E. E. ;

Poddubskaya, Elena ;

Antonia, Scott ;

Pluzanski, Adam ;

Vokes, Everett E. ;

Holgado, Esther ;

Waterhouse, David ;

Ready, Neal ;

Gainor, Justin ;

Aren Frontera, Osvaldo ;

Havel, Libor ;

Steins, Martin ;

Garassino, Marina C. ;

Aerts, Joachim G. ;

Domine, Manuel ;

Paz-Ares, Luis ;

Reck, Martin ;

Baudelet, Christine ;

Harbison, Christopher T. ;

Lestini, Brian ;

Spigel, David R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135

[5] The gasdermins, a protein family executing cell death and inflammation [J].

Broz, Petr ;

Pelegrin, Pablo ;

Shao, Feng .

NATURE REVIEWS IMMUNOLOGY, 2020, 20 (03) :143-157

[6] Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden [J].

Chalmers, Zachary R. ;

Connelly, Caitlin F. ;

Fabrizio, David ;

Gay, Laurie ;

Ali, Siraj M. ;

Ennis, Riley ;

Schrock, Alexa ;

Campbell, Brittany ;

Shlien, Adam ;

Chmielecki, Juliann ;

Huang, Franklin ;

He, Yuting ;

Sun, James ;

Tabori, Uri ;

Kennedy, Mark ;

Lieber, Daniel S. ;

Roels, Steven ;

White, Jared ;

Otto, Geoffrey A. ;

Ross, Jeffrey S. ;

Garraway, Levi ;

Miller, Vincent A. ;

Stephens, Phillip J. ;

Frampton, Garrett M. .

GENOME MEDICINE, 2017, 9

[7] Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade [J].

Charoentong, Pornpimol ;

Finotello, Francesca ;

Angelova, Mihaela ;

Mayer, Clemens ;

Efremova, Mirjana ;

Rieder, Dietmar ;

Hackl, Hubert ;

Trajanoski, Zlatko .

CELL REPORTS, 2017, 18 (01) :248-262

[8] Mutant BRAF and MEK Inhibitors Regulate the Tumor Immune Microenvironment via Pyroptosis [J].

Erkes, Dan A. ;

Cai, Weijia ;

Sanchez, Ileine M. ;

Purwin, Timothy J. ;

Rogers, Corey ;

Field, Conroy O. ;

Berger, Adam C. ;

Hartsough, Edward J. ;

Rodeck, Ulrich ;

Alnemri, Emad S. ;

Aplin, Andrew E. .

CANCER DISCOVERY, 2020, 10 (02) :254-269

[9] Pyroptosis: A new frontier in cancer [J].

Fang, Yuan ;

Tian, Shengwang ;

Pan, Yutian ;

Li, Wei ;

Wang, Qiming ;

Tang, Yu ;

Yu, Tao ;

Wu, Xi ;

Shi, Yongkang ;

Ma, Pei ;

Shu, Yongqian .

BIOMEDICINE & PHARMACOTHERAPY, 2020, 121

[10] Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data [J].

Finotello, Francesca ;

Mayer, Clemens ;

Plattner, Christina ;

Laschober, Gerhard ;

Rieder, Dietmar ;

Hackl, Hubert ;

Krogsdam, Anne ;

Loncova, Zuzana ;

Posch, Wilfried ;

Wilflingseder, Doris ;

Sopper, Sieghart ;

Ijsselsteijn, Marieke ;

Brouwer, Thomas P. ;

Johnson, Douglas ;

Xu, Yaomin ;

Wang, Yu ;

Sanders, Melinda E. ;

Estrada, Monica V. ;

Ericsson-Gonzalez, Paula ;

Charoentong, Pornpimol ;

Balko, Justin ;

de Miranda, Noel Filipe da Cunha Carvahlo ;

Trajanoski, Zlatko .

GENOME MEDICINE, 2019, 11 (1)

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