Theranostics 2021; 11(20):9884-9903. doi:10.7150/thno.63202 This issue Cite

Research Paper

Establishment of tumor inflammasome clusters with distinct immunogenomic landscape aids immunotherapy

Qingyu Liang1,#, Jianqi Wu1,#, Xin Zhao2,#, Shuai Shen1, Chen Zhu1, Tianqi Liu1, Xiao Cui1, Ling Chen3, Chunmi Wei4, Peng Cheng1, Wen Cheng1✉, Anhua Wu1✉

1. Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
2. Department of Basic Medicine, China Medical University, Shenyang, China.
3. Department of Neurosurgery, Chinese People's Liberation Army of China (PLA) General Hospital, Medical School of Chinese PLA, Institute of Neurosurgery of Chinese PLA, China.
4. Department of Radiotherapy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
#These authors contributed equally to this work.

Citation:
Liang Q, Wu J, Zhao X, Shen S, Zhu C, Liu T, Cui X, Chen L, Wei C, Cheng P, Cheng W, Wu A. Establishment of tumor inflammasome clusters with distinct immunogenomic landscape aids immunotherapy. Theranostics 2021; 11(20):9884-9903. doi:10.7150/thno.63202. https://www.thno.org/v11p9884.htm
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Abstract

Graphic abstract

Inflammasome signaling is a reaction cascade that influences immune response and cell death. Although the inflammasomes participate in tumorigenesis, their role as an oncogenic booster or a tumor suppresser is still controversial. Therefore, it is important to comprehensively investigate the inflammasome signaling status across various cancers to clarify its clinical and therapeutic significance.

Methods: A total of 9881 patients across 33 tumor types from The Cancer Genome Atlas database were included in this study. Five gene sets were identified to step-wisely profile inflammasome signaling. Unsupervised clustering was used for sample classification based on gene set enrichment. Machine learning and in vitro and in vivo experiments were used to confirm the implications of inflammasome classification.

Results: A hundred and forty-one inflammasome-signaling-related genes were identified to construct five gene sets representing the sensing, activation, and termination steps of the inflammasome signaling. Six inflammasome clusters were robustly established with distinct molecular, biological, clinical, and therapeutic features. Importantly, clusters with inflammasome signaling activation were found to be immunosuppressive and resistant to ICB treatment. Inflammasome inhibition reverted the therapeutic failure of ICB in inflammasome-activated tumors. Moreover, based on the proposed classification and therapeutic implications, an open website was established to provide tumor patients with comprehensive information on inflammasome signaling.

Conclusions: Our study conducted a systematical investigation on inflammasome signaling in various tumor types. These findings highlight the importance of inflammasome evaluation in tumor classification and provide a foundation for improving relevant therapeutic regimens.

Keywords: Inflammasome, tumor classification, prognosis, tumor-associated macrophages, immunotherapy


Citation styles

APA
Liang, Q., Wu, J., Zhao, X., Shen, S., Zhu, C., Liu, T., Cui, X., Chen, L., Wei, C., Cheng, P., Cheng, W., Wu, A. (2021). Establishment of tumor inflammasome clusters with distinct immunogenomic landscape aids immunotherapy. Theranostics, 11(20), 9884-9903. https://doi.org/10.7150/thno.63202.

ACS
Liang, Q.; Wu, J.; Zhao, X.; Shen, S.; Zhu, C.; Liu, T.; Cui, X.; Chen, L.; Wei, C.; Cheng, P.; Cheng, W.; Wu, A. Establishment of tumor inflammasome clusters with distinct immunogenomic landscape aids immunotherapy. Theranostics 2021, 11 (20), 9884-9903. DOI: 10.7150/thno.63202.

NLM
Liang Q, Wu J, Zhao X, Shen S, Zhu C, Liu T, Cui X, Chen L, Wei C, Cheng P, Cheng W, Wu A. Establishment of tumor inflammasome clusters with distinct immunogenomic landscape aids immunotherapy. Theranostics 2021; 11(20):9884-9903. doi:10.7150/thno.63202. https://www.thno.org/v11p9884.htm

CSE
Liang Q, Wu J, Zhao X, Shen S, Zhu C, Liu T, Cui X, Chen L, Wei C, Cheng P, Cheng W, Wu A. 2021. Establishment of tumor inflammasome clusters with distinct immunogenomic landscape aids immunotherapy. Theranostics. 11(20):9884-9903.

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