PDCD1

Overview

PDCD1 (PD-1) is an immune checkpoint receptor and the target of anti-PD-1 antibodies. In the corpus it is a component of the prognostic Immunologic Constant of Rejection (ICR) gene expression signature in colon cancer.

Alterations observed in the corpus

  • Component of the 20-gene ICR immunoregulatory counter-activation module used to classify 348 primary colon cancers in the AC-ICAM cohort; no PDCD1-specific mutation finding reported PMID:37202560.
  • Target of nivolumab; surface expression measured on peripheral blood T cells by multiparameter flow cytometry (22C3 pharmDx assay) in a phase 2 IMRT reirradiation trial (NCT03521570, n=51) in recurrent/second primary HNSC. Co-expression of PDCD1 (PD-1) with MKI67 (Ki-67) on CD4+ T cells was used as a pharmacodynamic biomarker; ≥1.5-fold increase from baseline at week 2 or 4 trended with worse PFS (HR 2.09, 95% CI 0.77–5.66, P = .14; median PFS 16.0 vs. 27.1 months). PMID:38780927
  • PDCD1 (PD1) progressively upregulated on CD8+ T cells from the STIC.I stage onward in HGSOC fallopian tube precursors; activation markers (Ki67+ or PD1+) rise from 11% in p53.I to 25–43% in STIC.I/STIC.C/cancer; exhaustion markers (LAG3+ or PD1+LAG3+) increase 3- to 7-fold; PDCD1 listed alongside LAG3, HAVCR2 (TIM3), and CTLA4 as exhaustion/checkpoint markers in this 44-specimen HGSOC spatial atlas. PMID:39386723
  • PD-1; marks antigen-experienced T cells in HGSOC; higher co-expression with CD274 in HRD subtypes PMID:36517593
  • PDCD1 (PD-1) expression on tumor-infiltrating lymphocytes is elevated in PBRM1-mutant ccRCC tumors with high immune cell infiltration, supporting use as an immunotherapy biomarker PMID:22138691
  • High expression of PD-1 (PDCD1) flagged as an immune-checkpoint-inhibitor rationale in metastatic neuroendocrine neoplasms (NENs) PN5, PN18, and PN19 within the whole-genome/transcriptome analysis (WGTA) precision-oncology cohort PMID:24326773
  • PD-1 expression is a defining marker of the immune-active HCC class; expression not predictive of response to nivolumab or pembrolizumab in HCC trials; anti-PD-1 has FDA accelerated approval in HCC PMID:24798001
  • PD-1 upregulated on T cells in non-keratinizing NPC due to chronic EBV antigen exposure; multiple anti-PD-1 mAbs approved or investigational in NPC (toripalimab, tislelizumab, penpulimab, pembrolizumab, nivolumab, sintilimab, serplulimab, tagitanlimab) PMID:24952746
  • PD-1 immune checkpoint whose blockade efficacy in biliary tract cancer is modulated by gut microbiota composition; Bacteroidetes enrichment improves anti-PD-1 outcomes while Proteobacteria dominance reduces sintilimab+anlotinib efficacy PMID:25608663
  • In cutaneous melanoma (SKCM), PDCD1 (PD-1) expression is elevated in the Immune transcriptomic subclass, which is associated with improved post-accession survival in regional-metastasis cases and high lymphocyte infiltration on pathology. PMID:26091043
  • Expression of PDCD1 (PD-1) did not significantly differ between anti-PD-1 responders and non-responders in pretreatment metastatic melanoma (n=28 RNA-seq subset, whole-tumor transcriptome); lack of significant difference attributed to dilution of immune-cell-specific signal in bulk RNA-seq. PMID:26997480
  • PDCD1 not directly altered in the 1,144-tumor NSCLC landscape study (660 lung ADC, 484 lung SqCC); 47% of lung ADC and 53% of lung SqCC had ≥5 predicted neoepitopes, providing rationale for broad checkpoint immunotherapy applicability across both subtypes. PMID:27158780
  • PDCD1 (PD-1) specifically upregulated in Cluster 3 of cholangiocarcinoma molecular subtypes alongside PDCD1LG2 (PD-L2) and BTLA, motivating immune-checkpoint blockade as a candidate therapeutic strategy in that subtype PMID:28667006
  • PDCD1 (PD-1) strongly expressed in luminal-infiltrated subtype of MIBC, the proposed checkpoint-immunotherapy-responsive subset; expression also high in basal-squamous PMID:28988769
  • PDCD1 (PD-1) upregulated on-therapy regardless of response in metastatic melanoma patients treated with nivolumab; pre-therapy expression not differentially expressed between responders/non-responders by RNA-seq, though PD-L1 IHC positivity selected for response among Ipi-P patients PMID:29033130

Cancer types (linked)

  • Colon adenocarcinoma (COAD) — part of ICR signature that outperforms CMS and MSI for prognosis PMID:37202560.
  • Head and neck squamous cell carcinoma (HNSC) — target of nivolumab; PD-1+Ki-67+CD4+ T-cell surge at week 2–4 paradoxically trended with worse PFS in 51-patient reirradiation trial, unlike in lung cancer and melanoma. PMID:38780927

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • ICR correlates with immunotherapy response in other tumor types per the authors, but predictive utility of PDCD1 expression for immune checkpoint blockade in colon cancer was not directly tested PMID:37202560.
  • In the ROBIN METEOR cervix cancer Project 1, CRT does not significantly upregulate the PD-1 (PDCD1)/PDL-1 axis in tumor cells; in the GenRad HNSCC MCT (NCT03521570), re-irradiation plus PD-1 inhibition (nivolumab) was effective in recurrent/second primary HNSCC, and shorter progression-free survival was associated with a 1.5-fold increase in PD1+Ki67+CD4+ T cells from baseline to week 2 or 4 of treatment PMID:41941260.
  • Nivolumab (anti-PD-1, anti-PDCD1) combined with IMRT reirradiation in recurrent/second primary HNSCC (NCT03521570, n=51): 1-year PFS 61.7% (95% CI 49.2%–77.4%), rejecting null of <43.8% (P = .002). Grade ≥3 treatment-related AEs in 11.8%; no grade 5 events. PMID:38780927

Open questions

  • Whether ICR-high COAD patients benefit preferentially from PD-1 blockade is untested in this cohort PMID:37202560.

Sources

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

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:25608663

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:28667006

This page was processed by entity-page-writer on 2026-05-15. - 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.