ArticleFrontiers in immunology2017
Association of CTLA-4 Gene Variants with Response to Therapy and Long-term Survival in Metastatic Melanoma Patients Treated with Ipilimumab: An Italian Melanoma Intergroup Study.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Association ofJournal of clinical medicine · 2026Article
- Regulatory polymorphisms ofJournal for immunotherapy of cancer · 2025Article
- Mapping the genetic landscape establishing a tumor immune microenvironment favorable for anti-PD-1 response.Cell reports · 2025Article
- Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.Journal for immunotherapy of cancer · 2025Review
- Association of Cytotoxic T-Lymphocyte Antigen-4 (International journal of molecular sciences · 2024Article
- Association ofCurrent issues in molecular biology · 2024Article
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- Dose Optimization in Oncology Drug Development: The Emerging Role of Pharmacogenomics, Pharmacokinetics, and Pharmacodynamics.Cancers · 2023Review
- Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response.Nature communications · 2023Article
- 'Know thyself' - host factors influencing cancer response to immune checkpoint inhibitors.The Journal of pathology · 2022Review
- Editorial: Decoding checkpoint inhibitor-induced endocrinopathies.Frontiers in endocrinology · 2022Article
- Advanced Nanotechnology for Enhancing Immune Checkpoint Blockade Therapy.Nanomaterials (Basel, Switzerland) · 2021Review
- Article
- Article
- Response to ipilimumab therapy in metastatic melanoma patients: potential relevance of CTLA-4Cancer immunology, immunotherapy : CII · 2020Article
- Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response.Journal of clinical medicine · 2020Review
- Melanoma and Vitiligo: In Good Company.International journal of molecular sciences · 2019Review
- Clinical Pharmacokinetic and Pharmacodynamic Considerations in the (Modern) Treatment of Melanoma.Clinical pharmacokinetics · 2019Review
- Pharmacogenetics of anticancer monoclonal antibodies.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study.Cancer immunology, immunotherapy : CII · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
31 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ipilimumab (IPI) blocks CTLA-4 immune checkpoint resulting in T cell activation and enhanced antitumor immunity. IPI improves overall survival (OS) in 22% of patients with metastatic melanoma (MM). We investigated the association of CTLA-4 single nucleotide variants (SNVs) with best overall response (BOR) to IPI and OS in a cohort of 173 MM patients. Patients were genotyped for six CTLA-4 SNVs (-1661A>G, -1577G>A, -658C>T, -319C>T, +49A>G, and CT60G>A). We assessed the association between SNVs and BOR through multinomial logistic regression (MLR) and the prognostic effect of SNVs on OS through Kaplan-Meier method. Both -1577G>A and CT60G>A SNVs were found significantly associated with BOR. In particular, the proportion of responders was higher in G/G genotype while that of stable patients was higher in A/A genotype. The frequency of patients experiencing progression was similar in all genotypes. MLR evidenced a strong downward trend in the probability of responsiveness/progression, in comparison to disease stability, as a function of the allele A "dose" (0, 1, or 2) in both SNVs with reductions of about 70% (G/A vs G/G) and about 95% (A/A vs G/G). Moreover, -1577G/G and CT60G/G genotypes were associated with long-term OS, the surviving patients being at 3 years 29.8 and 30.8%, respectively, as compared to 12.9 and 14.4% of surviving patients carrying -1577G/A and CT60G/A, respectively. MM patients carrying -1577G/G or CT60G/G genotypes may benefit from IPI treatment in terms of BOR and long-term OS. These CTLA-4 SNVs may serve as potential biomarkers predictive of favorable outcome in this subset of patients.
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