PDCD1LG2

Overview

PDCD1LG2 (Programmed Cell Death 1 Ligand 2, also known as PD-L2 or CD273) is an immune checkpoint ligand that binds PD-1 (PDCD1) on T cells to inhibit anti-tumor immune responses. In cancer, PDCD1LG2 is co-amplified with JAK2 and CD274 (PD-L1) at chromosome 9p24.1, providing a genomic rationale for immune checkpoint blockade in tumors harboring this amplification.

Alterations observed in the corpus

  • PDCD1LG2 co-amplified with JAK2 and CD274 at 9p24.1 in 15% of EBV-positive gastric tumors (EGC); associated with elevated mRNA expression; provides rationale for PD-L1/L2 immune checkpoint blockade and JAK2 inhibition in this subtype PMID:25079317
  • Tumor RNA expression of PDCD1LG2 (PD-L2) is significantly higher in clinical-benefit patients (P=0.041, Mann-Whitney) in a 110-patient metastatic melanoma cohort treated with ipilimumab; PD-L2 expression adds complementary information to DNA-level mutational burden PMID:26359337
  • Expression of PDCD1LG2 (PD-L2) did not significantly differ between anti-PD-1 responders and non-responders in pretreatment metastatic melanoma (n=28 RNA-seq subset); whole-tumor bulk transcriptome may dilute immune-cell-restricted signal. PMID:26997480
  • TERT::PDCD1LG2 interchromosomal rearrangement (patient 29) linking the TERT reverse-transcriptase domain exon 7 to intron 5 of PDCD1LG2; no expressed RNA fusion detected; clinically intriguing given PDL2’s role in PD-1 ligand biology PMID:28373299
  • PDCD1LG2 (PD-L2) specifically upregulated in Cluster 3 of cholangiocarcinoma molecular subtypes alongside PDCD1 (PD-1) and BTLA, motivating immune-checkpoint blockade as a candidate therapeutic strategy in that subtype PMID:28667006

Cancer types (linked)

  • EGC: 9p24.1 amplification (JAK2/CD274/PDCD1LG2) in 15% of EBV-positive subtype; elevated expression in amplified tumors; supports immune checkpoint therapy PMID:25079317

Co-occurrence and mutual exclusivity

  • Co-amplified with JAK2 and CD274 (PD-L1) at 9p24.1 in EBV-positive gastric cancer; this co-amplification is enriched in the EBV subtype relative to other gastric cancer subtypes PMID:25079317

Therapeutic relevance

  • 9p24.1 amplification provides mechanistic rationale for PD-L1/PD-L2 checkpoint blockade (anti-PD-1/PD-L1 antibodies) in EBV-positive gastric cancer; concurrent JAK2 amplification may further support JAK2 inhibitor evaluation in this genomic context PMID:25079317

Open questions

  • Whether PDCD1LG2 vs CD274 (PD-L1) expression levels differ in predicting response to PD-1/PD-L1 blockade within 9p24.1-amplified gastric tumors is not addressed.
  • Translational validation of anti-PD-L1/L2 efficacy in EBV-positive gastric cancer patients with 9p24.1 amplification remains for subsequent trials.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26359337

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

This page was processed by wiki-cli on 2026-05-14. - PMID:28373299

This page was processed by wiki-cli on 2026-05-14. - PMID:28667006

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