Programmed cell death protein 1
Programmed cell death protein 1 (PD-1), encoded by PDCD1, is an inhibitory immune-checkpoint receptor expressed primarily on activated immune cells, including T cells.
Programmed cell death protein 1 (PD-1), encoded by PDCD1, is an inhibitory immune-checkpoint receptor expressed primarily on activated immune cells, including T cells. Binding of PD-1 to its ligands, programmed death-ligand 1 (PD-L1; encoded by CD274) or PD-L2, attenuates signaling that promotes T-cell activation and effector function. This pathway contributes to immune tolerance and is frequently exploited within the tumor immune microenvironment to limit antitumor immune responses.
In cancer immunotherapy, antibodies that block PD-1 or PD-L1 can restore or enhance antitumor activity, particularly that of CD8-positive T cells. Anti-PD-1 therapy is therefore used alone or in combination with other approaches, including antibody–drug conjugates, antiangiogenic agents, therapeutic vaccines, targeted drugs, and agents intended to modify immunosuppressive tumor niches. Current research also addresses biomarkers of response and resistance, including PD-1/PD-L1 expression, soluble immune-checkpoint molecules, cytokine and chemokine profiles, tumor-cell mechanics, and factors associated with the tumor microenvironment.
Rebuilt from PubMed 18 Sept 2026 · no new papers today
Where the papers sit
19 papers study programmed cell death protein 1 directly. The themes below are drawn from those 19.
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T-Cell Dysfunction and Resistance : Work is moving toward explaining checkpoint resistance through hypoxic neutrophils, metabolic reprogramming, S100A10-driven CD8-positive T-cell exhaustion, disrupted cytotoxic lysis, and altered PD-1 signaling. 7 papers · 36.8%
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Immune Response in Carcinoma : Chemoimmunotherapy and chemoradiotherapy are being linked to CD8-positive T-cell activity, circulating cytokines, objective response, survival, and treatment-related adverse events across locally advanced carcinomas. 4 papers · 21.1%
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PD-1 Therapy Biomarkers : Biomarker research spans tumor mechanics, plasma-cell immunotherapy targets, proteomic and metabolomic signatures of immune-related adverse events, and IKZF2/IKZF4 degradation to target regulatory T cells. 4 papers · 21.1%
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PD-L1 Regulation and Targeting : PD-L1 research is expanding from expression and survival associations toward miRNA and PRKX-mediated regulation, structure-guided small-molecule inhibitors, and combination strategies involving TGFβ blockade and chemotherapy. 4 papers · 21.1%
Recent Findings on Programmed cell death protein 1
PD-1 Resistance and Immune Evasion: S100A10, PRKX, HIF1A+ CSF3R+ neutrophils, and LASP1 deficiency identify distinct routes to impaired anti-PD-1 responses across solid tumors 42732672Sep42716706Sep42711068Sep42686372Sep. S100A10 activates cPLA2-5-LOX-mediated arachidonic acid metabolism and ferroptosis-associated signaling, driving CD8+ T-cell exhaustion in hepatocellular carcinoma; its inhibition improves anti-PD-1 therapy. 42732672Sep PRKX phosphorylates PD-L1 at T285, recruits YWHAE, prevents UBE2M-mediated ubiquitination, and stabilizes PD-L1 in an immunosuppressive gastric cancer subtype 42716706Sep. In NSCLC, a hypoxic niche containing HIF1A+ CSF3R+ neutrophils, exhausted T cells, and stromal cells promotes senescence, glycolysis, and neoadjuvant therapy resistance; platycodin-D2, navitoclax, and anti-PD-1 improved tumor control in mice 42711068Sep. LASP1 deficiency instead disrupts Arp2/3-regulated cytoskeletal dynamics and lipid organization at the immunological synapse, while simvastatin restored anti-PD-1 sensitivity 42686372Sep. Conserved miRNAs and cancer-cell mechanical properties add candidate biomarkers, although miR-138-5p showed an opposite survival association from several other miRNAs, and tumor cell death trajectories varied by cell type 42616478Aug42535479Jul. QA9 extends this direction toward direct intervention by stabilizing the PD-L1 dimer while improving water solubility and adding antiangiogenic activity 42720488Sep.
Clinical Immunotherapy Outcomes: Tislelizumab, TP chemotherapy, and afatinib produced a 40.6% complete pathologic response rate, an 82.5% objective response rate, and a 97.3% 1-year overall survival rate in resectable locally advanced head and neck squamous cell carcinoma 42731876Sep. Increased intratumoral cytotoxic T lymphocytes and B cells were associated with pathologic response, while treatment increased peripheral CD8+ T cells and reduced B cells 42731876Sep. In pretreated metastatic triple-negative breast cancer, Trop-2 antibody-drug conjugates showed higher objective response rates and longer progression-free survival when combined with a PD-1 inhibitor, particularly with an added antiangiogenic agent, without increased severe toxicity 42714605Sep. Proteomic and metabolomic profiles linked immune-related adverse events after PD-1 blockade to NF-κB pathway involvement, altered SNRPA and CD63, an elevated kynurenine/tryptophan ratio, and lipid differences 42695906Sep. Plasma IL-10, CXCL9, CXCL13, sCD163, and soluble PD-1 tracked immune-desert, immune-excluded, and immune-inflamed phenotypes in head and neck squamous cell carcinoma, supporting biomarker-guided treatment and toxicity assessment 42684559Sep.
Tumor Immune Modulation: The PD-1 cytoplasmic domain directly inhibits T-cell receptor-induced LAT condensation through unphosphorylated tyrosines in its inhibitory motifs, whereas phosphorylation eliminates this inhibition 42721241Sep. BMS-986449 selectively degrades IKZF2 and IKZF4, suppresses tumors in humanized Cereblon knock-in mice, and produces stronger growth inhibition with anti-PD-1 therapy 42677819Sep. Oral bacterial membrane-hybridized nanovaccines use GP2-mediated M-cell transcytosis, dendritic cell reconfiguration, and CCR7-dependent trafficking to connect mucosal immunity with tumor control; PD-1 blockade further enhances effector mobilization and memory against rechallenge 42497859Jul. These approaches shift immune modulation toward signaling-condensate control, regulatory T-cell depletion, and mucosal-systemic vaccination alongside checkpoint inhibition.
Written from 19 PubMed abstracts, each one cited by PMID above. Published: 2026-09-11. Last written: 2026-09-15 by GPT. Drafted by language models from published abstracts; not medical advice.