Inhibiting MDM2 enhances RIPK3-mediated necroptosis and synergizes with immune checkpoint blockade therapy
T cell infiltration, leading to improved tumor control. In immunologically "cold" tumor models, combining MDM2 inhibition with anti-PD-1 blockade converted tumors to a T cell-inflamed state and significantly improved therapeutic efficacy, even in p53-deficient settings. These findings identify MDM2 as a regulator of TNF-α-induced necroptosis and highlight its potential as a therapeutic target for cancer immunotherapy.
Authors
- Hailin Tu (ORCID: https://orcid.org/0000-0002-9362-4343)
- Weihang Xiong
- Zexian Zeng (ORCID: https://orcid.org/0000-0002-3905-3244)
- Hanyang Yu
- Yingxin Wu
- Weili Liu
- Xin Lin (ORCID: https://orcid.org/0000-0003-0956-3654)
- Zongxu Zhang
Institutions
- Peking University (CN)
- Center for Life Sciences (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- iScience
- Published
- 2026-04-11
- DOI
- https://doi.org/10.1016/j.isci.2026.115724
- Primary Topic
- Cell death mechanisms and regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Tsinghua University
- Key Technologies Research and Development Program
- National Key Research and Development Program of China