CD274

Overview

CD274 (PD-L1) is an immune checkpoint ligand whose expression marks counter-regulation of adaptive anti-tumor immunity and is a target of PD-(L)1 blockade.

Alterations observed in the corpus

  • Included in the 20-gene Immunologic Constant of Rejection (ICR) signature as one of the immunoregulatory counter-activation genes, alongside CTLA4, FOXP3, IDO1, and PDCD1, applied to the 348-patient AC-ICAM colon cancer cohort PMID:37202560.
  • Tumor PD-L1 protein expression (CD274) measured by IHC with the 22C3 pharmDx assay (CPS scoring) in 51 recurrent/second-primary HNSCC patients treated with IMRT reirradiation + nivolumab; CPS <20 vs ≥20 did not predict PFS (68.8% vs 59.2% 1-year PFS, P = .86) or OS benefit, unlike the established predictive role of PD-L1 in R/M HNSCC with single-agent PD-1 blockade PMID:38780927.
  • CD274 (PDL1) protein expression used as a treatment-decision biomarker extracted by NLP pipelines for NSCLC patients in the MSK-CHORD real-world cohort (n=42,655 patients); PDL1+ vs PDL1− patients on immunotherapy showed a preserved OS benefit (HR ≈ 0.6) at scale PMID:39506116.
  • PD-L1; upregulated expression in HRD tumors (Cancer.cell.3 cluster) and adnexal HRD-Dup HGSOC tumors (P=2.8e-3) PMID:36517593
  • CD274 (PD-L1) expression levels identified as an immunotherapy biomarker in ccRCC molecular subtyping, correlating with immune infiltration patterns in TCGA KIRC cohort PMID:22138691
  • High expression (PD-L1) flagged as immune-checkpoint-inhibitor rationale in neuroendocrine neoplasm patients PN5, PN18, PN19 in WGTA-guided therapy study PMID:24326773
  • PD-L1 expression defines the immune-active class in HCC (~30% of tumors); IHC does not predict response to nivolumab or pembrolizumab in HCC trials PMID:24798001
  • PD-L1 upregulated in non-keratinizing NPC due to chronic EBV antigen exposure; multiple anti-PD-1/PD-L1 mAbs approved or investigational PMID:24952746
  • Co-amplified with JAK2 and PDCD1LG2 at 9p24.1 in 15% of EBV-positive gastric tumours; elevated mRNA expression provides mechanistic rationale for PD-L1/L2 immune-checkpoint blockade in EBV-positive gastric cancer PMID:25079317
  • No mutations or copy-number alterations in CD274 (PD-L1) or antigen-presentation pathway genes were associated with response or resistance to pembrolizumab in advanced NSCLC (34-patient cohort) PMID:25765070
  • Focal amplifications in BRAF-mutant melanoma subtype (PD-L1); relevant to pembrolizumab/nivolumab biomarker hypothesis PMID:26091043
  • CD274 (PD-L1) was not significantly differentially expressed between anti-PD-1 responders and non-responders in whole-tumor transcriptome of melanoma (n=28 RNA-seq), underscoring that checkpoint-molecule expression alone does not predict anti-PD-1 benefit in this cohort PMID:26997480.
  • CD274 (PD-L1) context: 47% of lung ADC and 53% of lung SqCC tumors had ≥5 predicted neoepitopes, supporting broad checkpoint immunotherapy applicability across NSCLC histologies regardless of PD-L1 expression PMID:27158780.
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  • Profiled in the antigen-presentation/immunology OncoPrint of 240 advanced NSCLC patients treated with anti-PD-(L)1 therapy; CD274 (PD-L1) alterations were tracked alongside TMB as an independent predictor of durable clinical benefit PMID:29337640

Cancer types (linked)

  • Colon adenocarcinoma — CD274 contributes to ICR clustering that prognostically stratifies AC-ICAM patients independent of CMS and MSI classifications PMID:37202560.
  • HNSC — PD-L1 CPS measured in recurrent/second-primary HNSCC (n=51) treated with IMRT reirradiation + nivolumab; CPS did not stratify benefit in this reirradiation context PMID:38780927.

Co-occurrence and mutual exclusivity

  • Co-expressed with Th1/cytotoxic effector genes in ICR-high colon tumors, reflecting the paradoxical coupling of inflammation and checkpoint counter-regulation PMID:37202560.

Therapeutic relevance

  • The paper references that ICR correlates with immunotherapy response in other tumor types but does not directly test PD-(L)1 blockade response in colon cancer PMID:37202560.
  • In the ROBIN METEOR center’s cervix cancer Project 1, CRT does not significantly upregulate the PDL-1 (CD274)/PD-1 axis in cervix tumor cells, in contrast to the p53/MDM2 axis which is upregulated; the ImmunoRad MCT further demonstrated that intensity-modulated re-irradiation combined with PD-1 inhibition (nivolumab) is tolerable and effective in recurrent/second primary HNSCC PMID:41941260.

Open questions

  • Whether CD274 expression drives or merely reports the ICR-high phenotype, and whether the mICRoScore predicts immune checkpoint blockade benefit, is not tested in this cohort PMID:37202560.
  • The failure of PD-L1 CPS to predict benefit with reirradiation + nivolumab suggests tumor PD-L1 expression may be a less reliable biomarker when PD-1 blockade is combined with reirradiation in a previously irradiated field PMID:38780927.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36517593

This page was processed by crosslinker on 2026-05-14. - PMID:22138691

This page was processed by crosslinker on 2026-05-14. - PMID:24326773

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:24952746

This page was processed by crosslinker on 2026-05-14. - PMID:25079317

This page was processed by crosslinker on 2026-05-14. - PMID:25765070

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:26997480

This page was processed by wiki-cli on 2026-05-14. - PMID:27158780

This page was processed by wiki-cli on 2026-05-14. - PMID:28988769

This page was processed by wiki-cli on 2026-05-15. - PMID:29033130

This page was processed by wiki-cli on 2026-05-15. - PMID:29100075

This page was processed by wiki-cli on 2026-05-15. - PMID:29337640

This page was processed by wiki-cli on 2026-05-15.