PD-L1

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PD-L1, also known as programmed death-ligand 1, is an immune checkpoint ligand that binds pd 1 to suppress antitumor T-cell responses and promote immune escape. It is widely studied across cancer immunotherapy, including colorectal cancer, gastric cancer, non-small cell lung cancer, cervical cancer, gallbladder cancer, breast cancer, nasopharyngeal carcinoma, and pancreatic adenosquamous carcinoma. Mechanistically, its expression is regulated by transcriptional and post-transcriptional programs such as etv5, znf652, nat10, ddx3, dhhc9, and prkd3, and it can be modulated by drugs or nanoplatforms that alter ubiquitin-proteasome degradation, trafficking, palmitoylation, or cell-surface presentation. Recent studies also highlight PD-L1 as a biomarker for immunotherapy response prediction, including PD-L1 combined positive score (CPS) ≥ 1, CT-based prediction, and comparison against newer models that outperform traditional PD-L1 stratification. Therapeutically, PD-L1 is directly targeted by agents such as durvalumab, atezolizumab, kl a167, and anti-PD-L1/L2 or bifunctional fusion proteins, with combination strategies involving radiotherapy, lenvatinib, STING agonism, and sympathetic signaling blockade. Overall, PD-L1 remains a central immune checkpoint marker and a major target for both direct blockade and indirect suppression of tumor immune evasion.

Cancer immunotherapy and resistance

  • PD-L1 expression correlated with prkd3 in a pan-cancer analysis, reinforcing its role as an immune checkpoint marker in tumor immunology. (PMID:41931575)
  • In colorectal cancer, PD-L1 was described as an immune checkpoint ligand that interacts with pd 1 to suppress antitumor T-cell responses. (PMID:41925220)
  • Low PD-L1 expression was associated with limited long-term efficacy in cervical cancer immunotherapy, highlighting its relevance to resistance. (PMID:41958269)
  • A pan-cancer XGBoost model outperformed traditional biomarkers such as PD-L1 for immunotherapy response prediction. (PMID:41925746)

Transcriptional and post-transcriptional regulation

  • etv5 directly bound and activated the PD-L1 promoter, linking PD-L1 upregulation to immune escape in gallbladder cancer. (PMID:41791643)
  • znf652 activated PD-L1 transcription, and phenethyl isothiocyanate downregulated PD-L1 in a concentration-dependent manner in hepatocellular carcinoma. (PMID:41983254)
  • nat10 increased PD-L1 expression via FOSB, contributing to cisplatin resistance and immune escape in gastric cancer. (PMID:41956987)
  • ddx3 regulated PD-L1 cell-surface presentation through 3′ untranslated region-dependent control, affecting checkpoint availability. (PMID:41881089)

Therapeutic targeting and combination strategies

  • PD-L1 was directly blocked by durvalumab and atezolizumab, including in non-small cell lung cancer and advanced endometrial cancer contexts. (PMID:41943281; PMID:41946650)
  • kl a167 was reported as a PD-L1 inhibitor in recurrent or metastatic nasopharyngeal carcinoma. (PMID:41989879)
  • A bifunctional anti-PD-L1/TGF-β fusion protein and a cytotoxic anti-PD-L1/L2 antibody both targeted PD-L1 to enhance antitumor activity. (PMID:41866914; PMID:41981447)
  • Combination approaches such as radiotherapy plus PD-L1 blockade with lenvatinib, and PD-1/PD-L1 blockade enhanced by sympathetic signaling inhibition, were reported to improve efficacy. (PMID:41481002; PMID:41850182)

Nanoplatforms, degradation, and trafficking control

  • Metformin-mediated ubiquitin-proteasome degradation downregulated PD-L1 in a nanoplatform study, showing a non-antibody route to checkpoint suppression. (PMID:41655906)
  • Deferasirox release from targeted nanoparticles reduced PD-L1, and PSMD14 targeting promoted PD-L1 degradation in breast cancer. (PMID:41940349; PMID:41981629)
  • BiNPs promoted lysosomal internalization and degradation of PD-L1, while fpPRPS reprogrammed PD-L1 trafficking to reduce T-cell inhibition. (PMID:41979280; PMID:41998161)
  • PD-L1 was also targeted by engineered nanoplatforms for homing and checkpoint inhibition, including dual-targeted tumor delivery systems. (PMID:41633299; PMID:41979280)

Biomarkers, imaging, and clinical context

  • PD-L1 was used as a biomarker for patient stratification, including PD-L1 IHC slides for positive tumor cell detection and the PD-L1 CPS ≥ 1 subgroup used in approval contexts. (PMID:42009323; PMID:41730003)
  • Chest CT-based models predicted PD-L1 expression in NSCLC, including a multi-task masked autoencoder with GAN augmentation and a clinician-deployable deep hypergraph model. (PMID:42020694; PMID:42008547)
  • PD-L1 was highlighted as a major research hotspot in esophageal cancer immunotherapy and as a comparator biomarker in ovarian cancer studies. (PMID:41722038; PMID:41841642)
  • In pancreatic adenosquamous carcinoma, high PD-L1 expression in the squamous component supported the rationale for immunotherapy. (PMID:41978418)