Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Sep 24, 2026

The tumor microenvironment (TME) shapes cancer initiation and progression through complex interactions among cancer cells and surrounding non-cancerous components. Cytokines, central immunomodulators secreted by immune cells, cancer-associated fibroblasts, and tumor cells, drive communication networks that affect tumor growth, metastasis, and immune suppression. Pyroptosis remodels the TME by promoting pro-inflammatory cytokine release and chronic inflammation, influencing immune escape and angiogenesis. This review addresses unresolved crosstalk among cytokines, pyroptosis, and TME, including therapy-associated complications, aiming to inform balanced therapeutic strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages37

Reading Time1 h 33 min

AccessFree to download

Abstract

Background

Tumor microenvironment and cytokine signaling

Pyroptosis-mediated remodeling

Wang et al. Molecular Cancer (2024) 23:268 [https://doi.org/10.1186/s12943-024-02183-9](https://doi.org/10.1186/s12943-024-02183-9) Molecular Cancer REVIEW Open Access Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication Hua Wang1,2†, Tao Wang1,2†, Shuxiang Yan3†, Jinxin Tang1,2, Yibo Zhang1,2, Liming Wang4*, Haodong Xu1,2,5* and Chao Tu1,2,6,7* Abstract In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes toTME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex interplay among cytokines, pyroptosis, and the TME, along with the dual effects of pyroptosison cancer progression and therapy-related complications like cytokine release syndrome. Unraveling these complexities could facilitate strategies that balance inflammatory responses while minimizing tissue damage during therapy. This review delves into the complex crosstalk between cytokines, pyroptosis, and the TME, elucidating their contribution to tumor progression and metastasis. By synthesizing emerging therapeutic targets and innovative technologies concerning TME, this review aims to provide novel insights that could enhance treatment outcomes for cancer patients. Keywords Pyroptosis, Cytokine, Tumor microenvironment, Mechanism, Clinical implication †Hua Wang, Tao Wang and Shuxiang Yan contributed equally to this work. *Correspondence: Liming Wang [wangliming@hnu.edu.cn](wangliming@hnu.edu.cn)[ ](wangliming@hnu.edu.cn)Haodong Xu [xuhaodong@csu.edu.cn](xuhaodong@csu.edu.cn)[ ](xuhaodong@csu.edu.cn)Chao Tu[tuchao@csu.edu.cn](tuchao@csu.edu.cn) 1 Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China 2 Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China 3 Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China 4 School of Biomedical Sciences, Hunan University, Changsha, Hunan 410011, China 5 Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA 6 Shenzhen Research Institute of Central South University, Guangdong 518063, China 7 Hunan Engineering Research Center of AI Medical Equipment, The Second Xiangya Hospital of Central, South University, Changsha, Hunan 410011, China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by

FAQs

What roles do the tumor microenvironment and cytokines play in cancer progression?

The TME supports tumor initiation and progression through interactions among cancer and non-cancer cells. Cytokines secreted within the TME coordinate communication networks that can promote tumor growth, metastasis, and immune suppression.

How does pyroptosis influence the tumor microenvironment?

Pyroptosis contributes to TME remodeling by driving the release of pro-inflammatory cytokines and sustaining chronic inflammation. It can affect immune escape and angiogenesis.

What challenges does the review highlight about targeting cytokines and pyroptosis in therapy?

The review emphasizes the complex interplay among cytokines, pyroptosis, and the TME, and notes dual effects where pyroptosis may both support cancer progression and contribute to therapy-related complications such as cytokine release syndrome.

Sep 24, 2026

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