PD-1

Byaibio

PD-1, also known as programmed cell death protein 1, is an immune checkpoint receptor and marker that helps restrain T-cell activity and maintain immune homeostasis. It functions mainly by binding PD-L1 to inhibit antitumor T-cell responses, and it is also discussed as a target for agonistic antibody strategies that promote immune tolerance. In cancer, PD-1 blockade is central to immunotherapy across melanoma, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, colorectal cancer, esophageal cancer, ovarian cancer, cervical cancer, non-small cell lung cancer, and Hodgkin lymphoma. Recent studies also link PD-1 expression to PRKD3 and NR1H4-dependent upregulation in CD8+ T cells, and show that dual targeting with LAG-3 or combination approaches can overcome exhaustion and resistance. Mechanistically, Fc-intact anti-PD-1 antibodies can deplete PD-1+ virus-specific CD8 T cells in the liver during chronic infection, highlighting that antibody format can alter biological outcome. Newer advances include bispecific agents, microbiome- and metabolite-based sensitization, and biomimetic nanoplatforms that enhance PD-1 blockade efficacy.

Cancer immunotherapy

  • PD-1/PD-L1 signaling is discussed in colorectal cancer immune evasion and therapy, underscoring PD-1 as a core checkpoint target in this disease context. (PMID:41925220)
  • Anti-PD-1 therapy is used in intrahepatic cholangiocarcinoma combination strategies, and HSP90 inhibition was reported to synergize with anti-PD-1 treatment. (PMID:41916296)
  • In melanoma, pembrolizumab-based combination therapy and anti-PD1 immunotherapy both targeted PD-1, with poor response linked to loss of tumor-infiltrating lymphocytes in IDH GOF mutant melanoma. (PMID:41732954; PMID:41955022)
  • PD-1 blockade was also highlighted in esophageal cancer immunotherapy research and in the POPCORN pre-operative checkpoint blockade study in NSCLC. (PMID:41722038; PMID:41957527)

Combination and resistance mechanisms

  • PD-1 and LAG-3 were described as synergizing to drive T-cell exhaustion and immune escape, supporting dual blockade to overcome immunotherapy resistance. (PMID:41846252)
  • NR1H4-dependent PD-1 upregulation in CD8+ T cells and PRKD3 correlation with PD-1 expression point to transcriptional and signaling programs linked to checkpoint regulation. (PMID:41780844; PMID:41931575)
  • Therapeutic blockade of LRG1 sensitized tumors to anti-PD-1 therapy, and icariin-induced Akkermansia enrichment improved PD-1 blockade efficacy in tumor mouse models. (PMID:41963620; PMID:42017465)
  • Lactobacillus johnsonii and nicotinic acid both enhanced sensitivity to PD-1 blockade, while NKG2A inhibition improved anticancer immunity in ovarian carcinoma when combined with PD-1 blockade. (PMID:41570324; PMID:41570324; PMID:41998001)

Therapeutic platforms and antibody engineering

  • Cadonilimab was described as a dual immune checkpoint inhibitor targeting PD-1 and CTLA-4, and ivonescimab simultaneously targets PD-1. (PMID:41954707; PMID:42012232)
  • PD-1 was targeted by pembrolizumab, nivolumab, penpulimab, and Fc-intact anti-PD-1 antibody therapy, illustrating the breadth of clinically relevant antibody formats. (PMID:41732954; PMID:41851965; PMID:41963080; PMID:41950082)
  • Fc-intact anti-PD-1 treatment caused depletion of PD-1+ virus-specific CD8 T cells in the liver during chronic infection, showing that Fc function can shape immune-cell depletion. (PMID:41950082)
  • PD-1-modified cell-membrane nanovesicles contributed to PD-L1-targeted tumor homing and checkpoint inhibition, and PD-1 was also incorporated into biomimetic nanoplatforms. (PMID:41633299)

Preclinical and translational advances

  • Anti-PD-1 therapy combined with ponatinib showed antitumor efficacy in mouse tumor models, and PD-1 blockade was also enhanced by Dualo-mvApDHsD/S for durable tumor eradication and long-term protection. (PMID:41946709; PMID:41973478)
  • Anti-PD-1 therapy was combined with NE@LTT@DNase1-based immunotherapy and with polyplex treatment, where intratumoral CD8+ T cells upregulated PD-1 and contributed to synergy. (PMID:41587524; PMID:41984833)
  • A humanized chimeric PD-1/PD-L1 mouse model was used to study renal effects of immune checkpoint inhibitors, supporting translational modeling of checkpoint toxicity. (PMID:41785046)
  • PD-1 was also targeted in studies of autoimmune hemolytic anemia and checkpoint-related nephritis, emphasizing its relevance beyond oncology. (PMID:41944848; PMID:41785046)