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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]
In the citing paper
“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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Citations
Cites
TNM Classification of Malignant Tumours
Hermanek, P., & Sobin, L. H. (1987) · Springer eBooks · doi:10.1007/978-3-642-82982-6 · Cited by 16,077
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Wnt/β-Catenin Signaling in Development and Disease
Clevers, H. (2006) · Cell · doi:10.1016/j.cell.2006.10.018 · Cited by 5,568
Gerdes, J., Lemke, H., Baisch, H., Wacker, H. H., Schwab, U., & Stein, H. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.4.1710 · Cited by 4,173
Enhancement of Antitumor Immunity by CTLA-4 Blockade
Leach, D. R., Krummel, M. F., & Allison, J. P. (1996) · Science · doi:10.1126/science.271.5256.1734 · Cited by 3,955
Applied Survival Analysis: Regression Modeling of Time-to-Event Data
Hosmer, D. W., Lemeshow, S. A., & May, S. J. (2008) · Cited by 3,030
Greenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115611 · Cited by 2,318
Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608
Histological Typing of Lung and Pleural Tumours
Travis, W. D., Colby, T. V., CORRIN, B., Shimosato, Y., & Brambilla, E. M. (1999) · Springer eBooks · doi:10.1007/978-3-642-60049-4 · Cited by 1,534
Krummel, M. F., & Allison, J. P. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2533 · Cited by 923
Applied Survival Analysis: Regression Modeling of Time to Event Data
Rao, P., Hosmer, D. W., & Lemeshow, S. A. (2000) · Journal of the American Statistical Association · doi:10.2307/2669422 · Cited by 878
Lymph node mapping and curability at various levels of metastasis in resected lung cancer
Naruke, T., Suemasu, K., & Ishikawa, S. (1978) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(19)39559-5 · Cited by 789
A MOLECULAR PERSPECTIVE OF CTLA-4 FUNCTION
Teft, W. A., Kirchhof, M. G., & Madrenas, J. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090535 · Cited by 526
Maker, A. V., Phan, G. Q., Attia, P., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., Haworth, L. R., Levy, C. L., et al. (2005) · Annals of Surgical Oncology · doi:10.1245/aso.2005.03.536 · Cited by 492
CTLA-4-Mediated Inhibition of Early Events of T Cell Proliferation
Brunner-Weinzierl, M. C., Chambers, C. A., Chan, F. K.-M., Hanke, J., Winoto, A., & Allison, J. P. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.10.5813 · Cited by 419
CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction
Contardi, E., Palmisano, G. L., Tazzari, P. L., Martelli, A. M., Falà, F., Fabbi, M., Kato, T., Lucarelli, E., Donati, D. M., Polito, L., et al. (2005) · International Journal of Cancer · doi:10.1002/ijc.21155 · Cited by 324
β-Catenin: A Pivot between Cell Adhesion and Wnt Signalling
Bienz, M. (2005) · Current Biology · doi:10.1016/j.cub.2004.12.058 · Cited by 310
Martin, B., Paesmans, M., Mascaux, C., Berghmans, T., Lothaire, P., Meert, A.-P., Lafitte, J. J., & Jp, S. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602233 · Cited by 280
Carreno, B. M., Bennett, F., Chau, T. A., Ling, V., Luxenberg, D. P., Jussif, J. M., Baroja, M. L., & Madrenas, J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.3.1352 · Cited by 268
Jain, N., Nguyen, H., Chambers, C. A., & Kang, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910341107 · Cited by 253
Kase, S., Sugio, K., Yamazaki, K., Okamoto, T., Yano, T., & Sugimachi, K. (2000) · PubMed · Cited by 199
β‐Catenin signaling in biological control and cancer
Gavert, N. S., & Ben‐Ze'ev, A. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21505 · Cited by 168
Releasing the Brake on the Immune System: Ipilimumab in Melanoma and Other Tumors
Tarhini, A. A., Lo, E., & Minor, D. R. (2010) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2010.0865 · Cited by 159
Pistillo, M. P. (2002) · Blood · doi:10.1182/blood-2002-06-1668 · Cited by 127
CTLA-4 is expressed by human monocyte-derived dendritic cells and regulates their functions
Laurent, S., Carrega, P., Saverino, D., Piccioli, P., Camoriano, M., Morabito, A., Dozin, B., Fontana, V., Simone, R., Mortara, L., et al. (2010) · Human Immunology · doi:10.1016/j.humimm.2010.07.007 · Cited by 121
Clinical Significance of Aminopeptidase N in Non–Small Cell Lung Cancer
Tokuhara, T., Hattori, N., Ishida, H., Hirai, T., Higashiyama, M., Kodama, K., & Miyake, M. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0338 · Cited by 111
Nagaraju, K., Raben, N., Villalba, M. L., Danning, C. L., Loeffler, L., Lee, E. Y., Tresser, N. J., Abati, A. D., Fetsch, P. A., & Plötz, P. H. (1999) · Clinical Immunology · doi:10.1006/clim.1999.4743 · Cited by 99
New Insights of CTLA-4 into Its Biological Function in Breast Cancer
Mao, H., Zhang, L., Yang, Y., Zuo, W., Bi, Y., Gao, W., Deng, B., Sun, J., Shao, Q., & Qu, X. (2010) · Current Cancer Drug Targets · doi:10.2174/156800910793605811 · Cited by 97
Liu, D., Huang, C., Kameyama, K., Hayashi, E., Yamauchi, A., Kobayashi, S., & Yokomise, H. (2001) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(00)02545-5 · Cited by 94
Merlo, A. C., Tenca, C., Fais, F., Battini, L., Ciccone, E., Grossi, C. E., & Saverino, D. (2005) · Clinical and Vaccine Immunology · doi:10.1128/cdli.12.6.705-712.2005 · Cited by 93
Expression of CTLA‐4 by Human Monocytes
Wang, X. ‐., Giscombe, R., Yan, Z., Heiden, T., Xu, D., & Lefvert, A. K. (2002) · Scandinavian Journal of Immunology · doi:10.1046/j.0300-9475.2001.01019.x · Cited by 90
Hamilton, N. H. R., Banyer, J., Hapel, A. J., Mahalingam, S., Ramsay, A. J., Ramshaw, I. A., & Thomson, S. A. (2002) · PubMed · Cited by 87
CTLA-4 Is a Direct Target of Wnt/β-Catenin Signaling and Is Expressed in Human Melanoma Tumors
Shah, K. V., Chien, A. J., Yee, C., & Moon, R. T. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.170 · Cited by 84
The CTLA-4 gene is expressed in placental fibroblasts
Kaufman, K. A. (1999) · Molecular Human Reproduction · doi:10.1093/molehr/5.1.84 · Cited by 83
ATM, CTLA4, MNDA, andHEM1in High versus Low CD38–Expressing B-Cell Chronic Lymphocytic Leukemia
Joshi, A. D., Hegde, G. V., Dickinson, J. D., Mittal, A. K., Lynch, J. C., Eudy, J. D., Armitage, J. O., Bierman, P. J., Bociek, R. G., Devetten, M. P., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0283 · Cited by 75
Differential expression of VASP in normal lung tissue and lung adenocarcinomas
Dertsiz, L. (2005) · Thorax · doi:10.1136/thx.2004.037622 · Cited by 58
Kosmaczewska, A., Ciszak, L., Suwalska, K., Wołowiec, D., & Frydecka, I. (2004) · Leukemia · doi:10.1038/sj.leu.2403588 · Cited by 48
Targeting Cytotoxic T-Lymphocyte Antigen 4 in Immunotherapies for Melanoma and Other Cancers
Page, D. B., Yuan, J. D., & Wolchok, J. D. (2010) · Immunotherapy · doi:10.2217/imt.10.21 · Cited by 23
[Expression and significance of gp96 and immune-related gene CTLA-4, CD8 in lung cancer tissues].
Zheng, H., Li, Y., Wang, X., Zhang, X., & Wang, X. (2010) · Europe PMC (PubMed Central) · doi:10.3779/j.issn.1009-3419.2010.08.08 · Cited by 9
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Dyck, L., & Mills, K. H. G. (2017) · European Journal of Immunology · doi:10.1002/eji.201646875 · Cited by 553
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Hung, A. L., Maxwell, R., Theodros, D., Belcaid, Z., Mathios, D., Luksik, A. S., Kim, E. S., Wu, A., Xia, Y., Garzón-Muvdi, T., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1466769 · Cited by 343
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Araghi, M., Mannani, R., Maleki, A. H., Hamidi, A., Rostami, S. M., Safa, S. H., Faramarzi, F., Khorasani, S., Alimohammadi, M., Tahmasebi, S., et al. (2023) · Cancer Cell International · doi:10.1186/s12935-023-02990-y · Cited by 374
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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