PD-1
PD-1 (programmed cell death protein 1), also known as PDCD1, is an inhibitory immune-checkpoint receptor involved in the regulation of T-cell activity.
PD-1 (programmed cell death protein 1), also known as PDCD1, is an inhibitory immune-checkpoint receptor involved in the regulation of T-cell activity. It is particularly relevant to interactions between T-lymphocytes and the tumor microenvironment, where PD-1 signaling can limit antitumor immune responses. Therapeutic blockade of the PD-1 axis—often through antibodies directed against PD-1 or its ligand PD-L1—forms a major class of cancer immunotherapy, including pembrolizumab-based treatment.
Current research is focused not only on releasing PD-1-mediated inhibition but also on determining why responses vary among patients and tumors. These efforts include attempts to restore CD8-positive T-cell function, modify tumor-cell signaling and metabolism, identify biomarkers associated with progression-free survival and overall survival, and combine PD-1 blockade with cytokines, epigenetic agents, radiation therapy, or other targeted treatments. PD-1-directed cellular therapies are also being investigated outside oncology, including approaches designed to selectively target pathogenic PD-1-positive CD4+ T cells.
Rebuilt from PubMed 18 Sept 2026 · no new papers today
Where the papers sit
15 papers study pd-1 directly. The themes below are drawn from those 15. 2 new directions follow.
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Immunotherapy Response in Cancer : Combination strategies pair PD-1/PD-L1 targeting with radiotherapy, epigenetic or cytokine therapy, metabolic selection, and microenvironmental reprogramming. The recurring aim is to overcome resistance and improve CD8+ T-cell responses, especially in lung cancer. 8 papers · 53.3%
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Immune Signaling and Metabolism : PD-1 biology is being linked to broader stress and immune-signaling circuits rather than receptor signaling alone. Recurring mechanisms include tyrosine-dependent condensates, PPM1D–mitochondrial damage–cGAS-STING, enfortumab-induced cell death, CAR T neuroinflammation, and interferon-driven tumor growth. 5 papers · 33.3%
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Immunosuppressive Cancer Signaling : Tumor-intrinsic and myeloid pathways are being targeted to relieve immunosuppression and improve immunotherapy. Mutant p53 represses SPP1 in KRAS-driven lung adenocarcinoma, while BLVRB targeting potentiates treatment in monocytic AML. 2 papers · 13.3%
PD-1 can inhibit T-cell signaling through unphosphorylated inhibitory-motif tyrosines rather than phosphorylation-dependent signaling
The study of PD-1 cytoplasmic inhibitory motifs and T-cell receptor-induced LAT condensates assumed the conventional phosphorylation-mediated model of PD-1 inhibition, but found that PD-1 directly blocks LAT condensation through unphosphorylated tyrosines, whereas phosphorylation abolishes this inhibition. This assigns PD-1 a phosphorylation-independent, structural role in disrupting signaling condensates and changes the mechanistic basis of its inhibitory activity. 42721241Sep
PD-1 can serve as a surface marker and CAR-T target for depleting pathogenic immune cells rather than merely being blocked to release antitumor immunity
The study of multiple-sclerosis-associated neuroinflammation developed PD-1-directed CAR T cells that selectively depleted pathogenic PD-1-positive CD4 T cells and locally released IL-10, thereby reprogramming the central nervous system immune environment and improving disease outcomes in mice. This gives PD-1 a targetable identity on pathogenic helper-like T cells and supports cell-mediated removal of those cells, rather than therapeutic inhibition of PD-1 signaling. 42480527Jul
Recent Findings on PD-1
Cancer Immunotherapy Resistance: Entinostat, N-803, and αPD-1 restored stem-like TCF1+CD8+ T-cell reservoirs and intratumoral immune niches in resistant models 42731874Sep. Tumor-cell OX40L similarly enhanced PD-1 blockade by co-stimulating T cells and promoting antigen presentation in Non-small cell lung cancer 42731877Sep. METTL14 inhibition, constitutively active CFL1, and the PD-L1-targeted small molecule N02 each improved treatment responses through distinct cancer-cell or cytoskeletal mechanisms 42562044Aug42586064Aug42447749Jul. Biomarker studies linked response to elevated BMI or MetS, lower PIV, higher CPS, and MerTK-targeted PET signals, although MetS associations depended largely on body mass 42711346Sep42379015Jun. In cT3-4N0M0 oral squamous cell carcinoma with imaging-negative nodes after neoadjuvant PD-1 inhibitor therapy, omitting cervical lymph node dissection did not significantly worsen cervical lymph node control, DFS, or OS 42419164Jul.
Immune Signaling Mechanisms: PD-1 directly inhibits TCR-induced LAT condensation through unphosphorylated tyrosines in its inhibitory motifs, challenging phosphorylation-based models of receptor signaling 42721241Sep. PPM1D inhibition and enfortumab vedotin instead increased antitumor activity by activating mitochondrial cGAS-STING-IFN signaling or inducing MMAE-mediated immunogenic cell death, respectively 42378680Jun42685702Sep. Chronic type II interferon produced a contrasting outcome by releasing ds-mtRNA, inducing type I interferon, increasing PGE2 synthesis, and promoting tumor growth; eliminating PGE2 restored anti-PD1 responsiveness 42721225Sep. Localized PD-1 CAR T cells redirected this receptor toward depletion of pathogenic PD-1+ CD4 T cells, IL-10 release, and reduced CNS inflammation in neuroinflammation models 42480527Jul. Together, these findings connect PD-1-related outcomes to condensate formation, mitochondrial integrity, immunogenic cell death, and tissue-specific immune reprogramming.
Myeloid Immunosuppression: BLVRB and SPP1 regulate myeloid immunosuppression through distinct transcriptional circuits that limit T-cell cytotoxicity 42742315Sep42726875Sep. BLVRB depletion or Tamibarotene treatment reduced immune-modulatory gene expression and enhanced CAR-T and anti-PD-1 antibody efficacy in monocytic AML, partly through MAFB 42742315Sep. In KRAS-mutant LUAD, mutant p53 and FOXA1 repressed SPP1, reducing MDSC recruitment and increasing CD8+ T-cell infiltration, while SPP1 blockade synergized with anti-PD-1 therapy 42726875Sep.
Written from 15 PubMed abstracts, each one cited by PMID above. Published: 2026-09-14. Last written: 2026-09-17 by GPT. Drafted by language models from published abstracts; not medical advice.