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Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer
Open accessAbstract
The role of CTLA-4 in negative regulation of T-cell mediated immune response is particularly well established. Much less is known about its expression and function in tumour cells, and to our knowledge, no data are available on its possible impact on prognosis of NSCLC patients. We investigated CTLA-4 expression and prognostic role in 81 patients with radically resected stage I-III NSCLC. The analysis was performed by tissue microarray immunohistochemistry, and the median H-score of 20 was used as a threshold to define CTLA-4 overexpressing tumours. Correlation with standard prognostic factors was performed by using absolute and relative fold change indexes. Hazard ratios (HR) and corresponding 95% confidence limits (95% CL) were computed through the Cox model. A higher frequency of CTLA-4 overexpression (>20) was found in non-squamous than in squamous NSCLC (52.8 vs. 35.7%) and in Ki67 ≤ 15 expressing tumours, as compared to those with Ki67 > 15 (51.5 vs. 38.7%). A reduced death rate was found in CTLA-4 overexpressing tumours (HR = 0.60, 95% CL = 0.28/1.23), and a further decrease was observed when considering tumours with CTLA-4 > 20 and Ki67 ≤ 15, in comparison with tumours with CTLA-4 ≤ 20 and Ki67 > 15 (HR = 0.41; 95% CL = 0.15/1.13). Our observational and exploratory study provides a first and promising indication for an independent prognostic effect of CTLA-4 overexpression in radically resected NSCLC. We presume that this effect relies on modulation of the interaction of microscopic disease with CTLA-4-ligands expressing cells leading to NSCLC cell death.
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“CTLA-4 may be expressed in tumor lesions on infiltrating Tregs or exhausted conventional T cells as well as tumor cells themselves (53, 54).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [53]
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“CTLA-4 blockade may also take effect at the tumor site as exhausted CTLA-4-expressing T cells and Tregs can accumulate within the tumor microenvironment (29, 53).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [53]
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Metadata
- Authors
- Salvi, S., Fontana, V., Boccardo, S., Merlo, D. F., Margallo, E., Laurent, S., Morabito, A., Rijavec, E., Dal Bello, M. G., Mora, M., Ratto, G. B., Grossi, F., Truini, M., & Pistillo, M. P.
- Affiliations
- Ospedale Policlinico San Martino (IT)
- Corresponding author
- Pistillo, Maria Pia
- Venue
- Cancer Immunology Immunotherapy
- Published
- 2012-02-09
- Volume
- 61
- Issue
- 9
- Pages
- 1463-1472
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC11029051
- OpenAlex
- W2008062915
- Cited by
- 133
- References
- 39
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 10 · 2023: 9 · 2022: 10 · 2021: 7 · 2020: 19 · 2019: 7 · 2018: 17 · 2017: 12 · 2016: 8 · 2015: 10 · 2014: 8 · 2013: 6
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Immunology Immunotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- Funders
- Alleanza Contro il Cancro
- Topics
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- CTLA-4, non-small cell lung cancer, prognostic factors, Ki-67, lung squamous cell carcinoma, radical resection, survival
- MeSH terms
- Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunohistochemistry, Lung Neoplasms, Male, Middle Aged, Prognosis, Prospective Studies, Survival Analysis, CTLA-4 Antigen
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