{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:18:29Z","timestamp":1787818709932,"version":"build-2784847793"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Disulfidptosis is a recently characterized regulated cell death pathway driven by disulfide stress. However, its immunological consequences in the tumor microenvironment remain poorly defined. In this review, we propose a conceptual framework in which disulfidptosis functions as an immunometabolic rheostat, wherein the net outcome\u2014T cell exhaustion versus immunogenic cell death\u2014is critically dependent on stress intensity, kinetics, and cellular context. We hypothesize that in glucose-deprived gastrointestinal tumors, chronic sub-lethal disulfide stress may erode CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell effector function through F-actin crosslinking at the immunological synapse, potentially involving STAT3\u2013LDHB\u2013G6PD-driven transcriptional reprogramming toward a TOX-associated exhaustion state. Conversely, acute synchronous tumor lysis releases damage-associated molecular patterns (DAMPs); however, productive dendritic cell (DC) cross-presentation requires that adenosine triphosphate (ATP)\/adenosine conversion and high mobility group box 1 (HMGB1) redox state meet quantitative thresholds. The DPP7\u2013GPX4 axis suppresses disulfidptosis to limit DAMP release and facilitate natural killer (NK) cell evasion, positioning it as a candidate innate immune checkpoint. We advance testable predictions for tuning this rheostat via timed nanodelivery, dietary sensitization, and DPP7\/GPX4 targeting, while explicitly distinguishing correlative biomarkers from causal mechanisms. Priority experiments to validate\u2014or falsify\u2014the rheostat hypothesis are outlined.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1932382","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:42:11Z","timestamp":1787816531000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Disulfidptosis as an immunometabolic rheostat in gastrointestinal cancers: tuning the balance between T Cell exhaustion and immunogenic cell death"],"prefix":"10.3389","volume":"14","author":[{"given":"Yachao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaijue","family":"Qiu","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China, School of Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency, The People\u2019s Hospital of Leshan","place":["Leshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s12672-025-01875-y","article-title":"Advances in the study of disulfidptosis in digestive tract tumors","volume":"16","author":"Chen","year":"2025","journal-title":"Discov. 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