Academic Journal
Latent effector capacity governs reversible T cell exhaustion: A theoretical mathematical model of PD-1 blockade response.
| Τίτλος: | Latent effector capacity governs reversible T cell exhaustion: A theoretical mathematical model of PD-1 blockade response. |
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| Συγγραφείς: | Liew AY; Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA., Li Y; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA., Dong H; Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.; Department of Urology, Mayo Clinic, Rochester, MN, USA. |
| Πηγή: | Science advances [Sci Adv] 2026 Oct 16; Vol. 12 (42), pp. eaei0840. Date of Electronic Publication: 2026 Oct 16. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
| Ιατρικοί όροι (MeSH): | T-Cell Exhaustion*/immunology , Programmed Cell Death 1 Receptor*/antagonists & inhibitors , Programmed Cell Death 1 Receptor*/metabolism , Immune Checkpoint Inhibitors*/pharmacology , Immune Checkpoint Inhibitors*/therapeutic use , T-Lymphocytes*/immunology , T-Lymphocytes*/metabolism , Models, Theoretical*, Neoplasms/immunology ; Neoplasms/drug therapy ; Humans ; Signal Transduction |
| Περίληψη: | T cell exhaustion is often viewed as a terminal state marked by irreversible loss of function during chronic infection and cancer. However, the rapid recovery of antitumor activity in clinical responders after PD-1 blockade suggests that some exhausted T cells retain hidden functional potential. To explain this paradox, we present a theoretical framework that separates latent effector capacity from active effector function. Latent effector capacity represents a history-dependent state reflecting preserved epigenetic accessibility and regulatory readiness, distinct from ongoing gene expression. In this model, PD-1 signaling acts as a reversible mask that suppresses effector function without eliminating the underlying effector capacity. The framework explains preserved chromatin accessibility, rapid reinvigoration after checkpoint blockade, and variable therapeutic responses. By incorporating nonlinear maintenance and erosion of latent effector capacity, the model predicts a bistable system with a point of no return beyond which exhaustion becomes irreversible. These principles may guide development of mechanistically informed biomarkers and artificial intelligence models predicting response to PD-1 therapy. |
| Substance Nomenclature: | 0 (Programmed Cell Death 1 Receptor) 0 (Immune Checkpoint Inhibitors) 0 (PDCD1 protein, human) |
| Entry Date(s): | Date Created: 20261016 Date Completed: 20261016 Latest Revision: 20261016 |
| Update Code: | 20261017 |
| DOI: | 10.1126/sciadv.aei0840 |
| PMID: | 42886782 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2375-2548 |
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| DOI: | 10.1126/sciadv.aei0840 |