Cell ResearchPub Date : 2026-10-21DOI: 10.1038/s41422-026-01311-y
Samir Zaidi, Charles L Sawyers
{"title":"Expanding DepMap: is the juice worth the squeeze?","authors":"Samir Zaidi, Charles L Sawyers","doi":"10.1038/s41422-026-01311-y","DOIUrl":"https://doi.org/10.1038/s41422-026-01311-y","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":31.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2026-10-21DOI: 10.1038/s41422-026-01310-z
Nagela G Zanluqui, Yvonne L Latour, Dorian B McGavern
{"title":"A neighborhood watch within the skull.","authors":"Nagela G Zanluqui, Yvonne L Latour, Dorian B McGavern","doi":"10.1038/s41422-026-01310-z","DOIUrl":"https://doi.org/10.1038/s41422-026-01310-z","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":31.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2026-10-20DOI: 10.1038/s41422-026-01306-9
Rui Kang, Xin Chen, Guido Kroemer, Daolin Tang
{"title":"Metabolic hallmarks of regulated cell death.","authors":"Rui Kang, Xin Chen, Guido Kroemer, Daolin Tang","doi":"10.1038/s41422-026-01306-9","DOIUrl":"https://doi.org/10.1038/s41422-026-01306-9","url":null,"abstract":"<p><p>Regulated cell death (RCD) is characterized by distinct molecular execution mechanisms, but its initiation, progression, and biological consequences are increasingly recognized as being shaped by cellular metabolism. Bioenergetic state, redox homeostasis, nutrient availability, metal ion metabolism, inflammatory metabolism, and organelle function collectively determine cellular susceptibility to death and influence the activation and execution of diverse RCD programs. In this review, we synthesize the metabolic hallmarks of established, independently validated, and recently proposed forms of RCD, highlighting both their mechanistic diversity and their extensive metabolic convergence. We then examine the endogenous mechanisms that maintain metabolic homeostasis and discuss how their disruption reshapes cell death responses in human disease and therapeutic contexts. Together, these insights provide a guide to the metabolic landscape of RCD and reveal metabolism not only as a modifier of cell death, but as a fundamental determinant of when, how, and with what consequences cells die. We conclude by discussing key conceptual and mechanistic challenges and emerging opportunities for therapeutically exploiting the metabolic control of RCD.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":31.1,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2026-10-08DOI: 10.1038/s41422-026-01304-x
Ivan Zanoni
{"title":"No time to die: cell death predicts IBD relapse.","authors":"Ivan Zanoni","doi":"10.1038/s41422-026-01304-x","DOIUrl":"https://doi.org/10.1038/s41422-026-01304-x","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":31.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2026-09-30DOI: 10.1038/s41422-026-01293-x
Xinyan Li, Peicheng Jiang, Huan Yin, Zhenyu Huo, Xin Xu, Somaira Nowsheen, Khaled Aziz, Sufei Zheng, Nan Sun, Bin Chen, Zhenkun Lou, Min Deng
{"title":"Ursodeoxycholic acid enhances cancer radioimmunotherapy by releasing a human-biased FXR-TRIM22-STAT1 immune brake.","authors":"Xinyan Li, Peicheng Jiang, Huan Yin, Zhenyu Huo, Xin Xu, Somaira Nowsheen, Khaled Aziz, Sufei Zheng, Nan Sun, Bin Chen, Zhenkun Lou, Min Deng","doi":"10.1038/s41422-026-01293-x","DOIUrl":"https://doi.org/10.1038/s41422-026-01293-x","url":null,"abstract":"<p><p>Radiotherapy is a fundamental modality in cancer treatment, used in the management of more than half of cancer patients. Beyond direct cytotoxicity, ionizing radiation activates innate immune pathways and inflammatory cytokines required for local tumor control and systemic (abscopal) responses. Yet in human tumors, DNA damage-induced immune activation is attenuated compared with the robust responses observed in mice, suggesting a human-biased checkpoint that constrains radioimmunity. Here, we identify a tumor-intrinsic, human-biased farnesoid X receptor (FXR)-tripartite motif containing 22 (TRIM22)-STAT1 proteostatic checkpoint that suppresses radiation-induced type I interferon signaling. Ionizing radiation stabilizes FXR, a nuclear receptor, through ubiquitin-specific peptidase 7 (USP7)-dependent deubiquitination, enabling FXR to transcriptionally induce the E3 ligase TRIM22. TRIM22 selectively binds STAT1 and catalyzes its K48-linked ubiquitination and degradation, extinguishing interferon-stimulated gene (ISG) programs downstream of cGAS-STING signaling. This regulatory circuit is absent in murine tumor cells, which lack a TRIM22 family member capable of destabilizing STAT1, providing a mechanistic explanation for the stronger radiation-induced immune responses observed in mice. Genetic disruption of FXR or TRIM22 preserves STAT1, amplifies type I interferon signaling, and enhances CD8⁺ T-cell activation and abscopal tumor control in peripheral blood mononuclear cell-humanized mice. Pharmacologic modulation of this pathway with ursodeoxycholic acid, a bile acid used clinically with reported FXR-antagonistic activity, suppresses radiation-induced TRIM22, restores STAT1-ISG signaling, and potentiates radiotherapy alone or with anti-PD-1 without overt toxicity in humanized models. Collectively, these findings define a human-biased checkpoint that limits radiotherapy-induced immunity and is absent in murine tumor cells, and highlight the FXR-TRIM22-STAT1 axis as an actionable target to enhance cancer radioimmunotherapy.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":31.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}