CTLA4

Overview

CTLA4 is an immune checkpoint receptor on T cells whose engagement dampens T-cell activation; it is a clinically validated target of ipilimumab-class immunotherapies.

Alterations observed in the corpus

  • Included in the 20-gene Immunologic Constant of Rejection (ICR) signature as an immunoregulatory counter-activation gene, alongside CD274, FOXP3, IDO1, and PDCD1, applied to the 348-patient AC-ICAM colon cancer cohort PMID:37202560.
  • CTLA4 RNA progressively upregulated on CD8+ T cells from STIC.I through STIC.C and invasive HGSOC, alongside LAG3 and HAVCR2, reflecting stepwise T-cell exhaustion across the HGSOC precursor-to-cancer progression axis PMID:39386723.
  • Target of tremelimumab (phase II ORR 17.6% in 20 HCC patients) and ipilimumab in combination ICI regimens for HCC PMID:24798001
  • Compensatory checkpoint in NPC; targeted by IBI-310 (+ sintilimab) and bispecifics (cadonilimab PD-1×CTLA-4; QL1706; SI-B003; vudalimab) PMID:24952746
  • Target of ipilimumab and tremelimumab; CTLA-4 blockade activates effector and helper T cells and depletes regulatory T cells, enabling antitumor immunity; neoantigen mutational load in tumors predicts survival benefit from anti-CTLA-4 therapy in melanoma PMID:25409260
  • Tumor RNA expression of CTLA4 significantly higher in metastatic melanoma patients with clinical benefit from ipilimumab vs. no benefit (P = 0.033, Mann-Whitney), indicating that CTLA4 expression in the tumor microenvironment is associated with immune checkpoint therapy response PMID:26359337
  • CTLA4 was not significantly differentially expressed between anti-PD-1 responders and non-responders in whole-tumor transcriptome analysis of melanoma (n=28), demonstrating that checkpoint-molecule expression does not distinguish anti-PD-1 response in this cohort; IPRES did not distinguish anti-CTLA-4 responders from non-responders in the Van Allen cohort PMID:26997480.
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Cancer types (linked)

  • Colon adenocarcinoma — CTLA4 expression contributes to ICR-based stratification that outperforms CMS and MSI for prognosis PMID:37202560.
  • OV (HGSOC) — CTLA4 upregulated on exhausted CD8+ T cells in STIC.I, STIC.C, and invasive cancer; marks progressive immune suppression preceding invasion PMID:39386723.

Co-occurrence and mutual exclusivity

  • Co-expressed with other ICR Th1/cytotoxic and checkpoint genes in ICR-high colon tumors PMID:37202560.

Therapeutic relevance

  • The paper references ICR’s correlation with immunotherapy response in other tumor types but does not directly test CTLA4 blockade in colon cancer PMID:37202560.

Open questions

  • Whether ICR-high, CTLA4-expressing colon tumors respond to checkpoint blockade is not tested in this cohort PMID:37202560.

Sources

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:25409260

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: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.