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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CTLA-4 may be expressed in tumor lesions on infiltrating Tregs, exhausted conventional T cells, and tumor cells themselves.
“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]
CTLA-4 blockade may also take effect at the tumor site because exhausted CTLA-4-expressing T cells and Tregs can accumulate within the tumor microenvironment.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
TNM Classification of Malignant Tumours
Hermanek, P., & Sobin, L. H. (1987) · Springer eBooks · doi:10.1007/978-3-642-82982-6 · Cited by 16,073 · see citing works
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 · see citing works
Wnt/β-Catenin Signaling in Development and Disease
Clevers, H. (2006) · Cell · doi:10.1016/j.cell.2006.10.018 · Cited by 5,568 · see citing works
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 · see citing works
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 · see citing works
Applied Survival Analysis: Regression Modeling of Time-to-Event Data
Hosmer, D. W., Lemeshow, S. A., & May, S. J. (2008) · Cited by 3,030 · see citing works
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 · see citing works
Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608 · see citing works
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 · see citing works
Krummel, M. F., & Allison, J. P. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2533 · Cited by 923 · see citing works
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 876 · see citing works
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 · see citing works
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 518 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 277 · see citing works
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 · see citing works
Jain, N., Nguyen, H., Chambers, C. A., & Kang, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910341107 · Cited by 256 · see citing works
Kase, S., Sugio, K., Yamazaki, K., Okamoto, T., Yano, T., & Sugimachi, K. (2000) · PubMed · Cited by 199 · see citing works
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 164 · see citing works
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 · see citing works
Pistillo, M. P. (2002) · Blood · doi:10.1182/blood-2002-06-1668 · Cited by 127 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 91 · see citing works
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 · see citing works
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 · see citing works
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 81 · see citing works
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 · see citing works
Differential expression of VASP in normal lung tissue and lung adenocarcinomas
Dertsiz, L. (2005) · Thorax · doi:10.1136/thx.2004.037622 · Cited by 58 · see citing works
Kosmaczewska, A., Ciszak, L., Suwalska, K., Wołowiec, D., & Frydecka, I. (2004) · Leukemia · doi:10.1038/sj.leu.2403588 · Cited by 48 · see citing works
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 · see citing works
[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 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations
Seidel, J. A., Otsuka, A., & Kabashima, K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00086 · Cited by 1,360 · see citing works
Immune checkpoints and their inhibition in cancer and infectious diseases
Dyck, L., & Mills, K. H. G. (2017) · European Journal of Immunology · doi:10.1002/eji.201646875 · Cited by 541 · see citing works
Lung Cancer Staging and Prognosis
Woodard, G. A., Jones, K. D., & Jablons, D. M. (2016) · Cancer treatment and research · doi:10.1007/978-3-319-40389-2_3 · Cited by 366 · see citing works
TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM
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 337 · see citing works
Recent advances in non-small cell lung cancer targeted therapy; an update review
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 352 · see citing works
Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier
Vafaei, S., Zekiy, A. O., Khanamir, R. A., Zaman, B. A., Ghayourvahdat, A., Azimizonuzi, H., & Zamani, M. (2022) · Cancer Cell International · doi:10.1186/s12935-021-02407-8 · Cited by 278 · see citing works
Remark, R., Becker, C., Gomez, J. E., Damotte, D., Dieu‐Nosjean, M., Sautès‐Fridman, C., Fridman, W. H., Powell, C. A., Altorki, N. K., Mérad, M., et al. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201409-1671pp · Cited by 270 · see citing works
Li, J., Jie, H.-B., Lei, Y. L., Gildener‐Leapman, N., Trivedi, S., Green, T., Kane, L., & Ferris, R. L. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1215 · Cited by 252 · see citing works
Immune checkpoint inhibitors: The linchpins of modern immunotherapy
Wilky, B. A. (2019) · Immunological Reviews · doi:10.1111/imr.12766 · Cited by 210 · see citing works
Evolving Roles for Targeting CTLA-4 in Cancer Immunotherapy
Zhao, Y., Yang, W., Huang, Y., Cui, R., Li, X., & Li, B. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000490025 · Cited by 180 · see citing works
Laurent, S., Queirolo, P., Boero, S., Salvi, S., Piccioli, P., Boccardo, S., Minghelli, S., Morabito, A., Fontana, V., Pietra, G., et al. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-108 · Cited by 163 · see citing works
Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types
Oyewole-Said, D., Konduri, V., Vazquez‐Perez, J., Weldon, S. A., Levitt, J. M., & Decker, W. K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.608024 · Cited by 134 · see citing works
Yuan, Y. (2014) · Journal of The Royal Society Interface · doi:10.1098/rsif.2014.1153 · Cited by 126 · see citing works
Lin, C., Chen, X., Li, M., Liu, J., Qi, X., Yang, W., Zhang, H., Cai, Z., Dai, Y., & Ouyang, X. (2015) · Clinical Lung Cancer · doi:10.1016/j.cllc.2015.02.002 · Cited by 119 · see citing works
The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors
Jia, X., Geng, L., Jiang, P., Xu, H., Nan, K., Yao, Y., Jiang, L., Sun, H., Qin, T., & Guo, H. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01749-x · Cited by 119 · see citing works
Teng, F., Meng, X., Kong, L., Mu, D., Zhu, H., Liu, S., Zhang, J., & Yu, J. (2015) · Translational research · doi:10.1016/j.trsl.2015.06.019 · Cited by 117 · see citing works
Immunotherapy in the treatment of non-small cell lung cancer
Sundar, R., Soong, R., Cho, B. C., Brahmer, J. R., & Soo, R. A. (2014) · Lung Cancer · doi:10.1016/j.lungcan.2014.05.005 · Cited by 113 · see citing works
CTLA-4 correlates with immune and clinical characteristics of glioma
Liu, F., Huang, J., Liu, X., Cheng, Q., Luo, C., & Liu, Z. (2020) · Cancer Cell International · doi:10.1186/s12935-019-1085-6 · Cited by 115 · see citing works
Yang, Z., & Tam, K. Y. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.22955 · Cited by 105 · see citing works
Karpathiou, G., Casteillo, F., Giroult, J.-B., Forest, F., Fournel, P., Monaya, A., Froudarakis, Μ. E., Dumollard, J. M., Prades, J. M., & Péoc’h, M. (2016) · Oncotarget · doi:10.18632/oncotarget.14242 · Cited by 102 · see citing works
ImmunoPET Imaging of CTLA-4 Expression in Mouse Models of Non-small Cell Lung Cancer
Ehlerding, E. B., England, C. G., Majewski, R. L., Valdovinos, H. F., Jiang, D., Liu, G., McNeel, D. G., Nickles, R. J., & Cai, W. (2017) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.7b00056 · Cited by 100 · see citing works
Cortiula, F., Reymen, B. J. T., Peters, S., Mol, P. V., Wauters, E., Vansteenkiste, J., Ruysscher, D. D., & Hendriks, L. E. L. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.06.013 · Cited by 99 · see citing works
Prognostic significance of immune cells in non-small cell lung cancer: meta-analysis
Soo, R. A., Chen, Z., Teng, R. S. Y., Tan, H.-L., Iacopetta, B. J., Tai, B. C., & Soong, R. (2018) · Oncotarget · doi:10.18632/oncotarget.24835 · Cited by 98 · see citing works
Tumor CTLA-4 overexpression predicts poor survival in patients with nasopharyngeal carcinoma
Huang, P.-Y., Guo, S.-S., Zhang, Y., Lu, J.-B., Chen, Q.-Y., Tang, L.-Q., Zhang, L., Liu, L.-T., Zhang, L., & Mai, H.-Q. (2016) · Oncotarget · doi:10.18632/oncotarget.7421 · Cited by 96 · see citing works
Paulsen, E., Kilvaer, T. K., Rakaee, M., Richardsen, E. H., Hald, S. M., Andersen, S., Busund, L., Bremnes, R. M., & Dønnem, T. (2017) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-017-2039-2 · Cited by 99 · see citing works
(IMI), O. B. O. T. I. M. I., Pistillo, M. P., Fontana, V., Morabito, A., Dozin, B., Laurent, S., Carosio, R., Banelli, B., Ferrero, F., Spano, L., et al. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2258-1 · Cited by 90 · see citing works
DNA damaging agents and DNA repair: From carcinogenesis to cancer therapy
de Almeida, L. C., Calil, F. A., Machado‐Neto, J. A., & Costa-Lotufo, L. V. (2020) · Cancer Genetics · doi:10.1016/j.cancergen.2020.12.002 · Cited by 86 · see citing works
Wei, D., Chen, W., Meng, R.-M., Zhao, N., Zhang, X., Liao, D., & Chen, G. (2018) · Respiratory Research · doi:10.1186/s12931-018-0843-7 · Cited by 85 · see citing works
Tumour cell‐intrinsic CTLA 4 regulates PD ‐L1 expression in non‐small cell lung cancer
Zhang, H., Dutta, P., Liu, J., Sabri, N., Song, Y., Li, W. X., & Li, J. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13956 · Cited by 83 · see citing works
Basu, B., Chakraborty, J., Chandra, A., Katarkar, A., Baldevbhai, J., Chowdhury, D. D., Ray, J. G., Chaudhuri, K., & Chatterjee, R. (2017) · Clinical Epigenetics · doi:10.1186/s13148-017-0314-x · Cited by 64 · see citing works
Sherafat, N. S., Keshavarz, A., Mardi, A., Mohammadiara, A., Aghaei, M., Maleki, L. A., & Mohammadi, M. H. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01751-7 · Cited by 66 · see citing works
Catacchio, I., Scattone, A., Silvestris, N., & Mangia, A. (2018) · Translational Oncology · doi:10.1016/j.tranon.2018.04.006 · Cited by 58 · see citing works
Biomarkers in Early-Stage Non-Small Cell Lung Cancer: Current Concepts and Future Directions
Burotto, M., Thomas, A., Subramaniam, D. S., Giaccone, G., & Rajan, A. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000302 · Cited by 62 · see citing works
Schlößer, H., Drebber, U., Kloth, M. T., Thelen, M., Rothschild, S. I., Haase, S., Garcia-Marquez, M. A., Wennhold, K., Berlth, F., Urbanski, A., et al. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1100789 · Cited by 59 · see citing works
Kassardjian, A., Shintaku, P. I., & Moatamed, N. A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195958 · Cited by 57 · see citing works
Hu, P., Liu, Q., Deng, G., Zhang, J., Liang, N., Xie, J., & Zhang, J. (2017) · Scientific Reports · doi:10.1038/srep42913 · Cited by 54 · see citing works
Tripathi, S. K., Pandey, K., Rengasamy, K. R. R., & Biswal, B. K. (2020) · Medicinal Research Reviews · doi:10.1002/med.21700 · Cited by 52 · see citing works
Chang, H., Jung, W. Y., Kang, Y., Lee, H., Kim, A., Kim, H. K., Shin, B. K., & Kim, B. (2016) · Oncotarget · doi:10.18632/oncotarget.12603 · Cited by 52 · see citing works
Ma, Y., Liu, X., Zhu, J., Li, W., Guo, L., Han, X., Song, B., Cheng, S., & Liu, J. (2015) · PubMed · Cited by 51 · see citing works
Role of CTLA4 in the Proliferation and Survival of Chronic Lymphocytic Leukemia
Mittal, A. K., Chaturvedi, N. K., Rohlfsen, R. A., Gupta, P., Joshi, A. D., Hegde, G. V., Bociek, R. G., & Joshi, S. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070352 · Cited by 50 · see citing works
The Resistance Mechanisms of Checkpoint Inhibitors in Solid Tumors
Koustas, E., Sarantis, P., Papavassiliou, A. G., & Karamouzis, M. V. (2020) · Biomolecules · doi:10.3390/biom10050666 · Cited by 50 · see citing works
Guo, X.-J., Lu, J., Zeng, H., Zhou, R., Sun, Q., Yang, G., Pei, Y.-Z., Meng, X., Shen, Y., Zhang, P., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.705378 · Cited by 48 · see citing works
Overcoming Tumor-Mediated Immunosuppression
Schlößer, H., Theurich, S., Shimabukuro‐Vornhagen, A., Holtick, U., Stippel, D. L., & von Bergwelt‐Baildon, M. (2014) · Immunotherapy · doi:10.2217/imt.14.58 · Cited by 48 · see citing works
Roncella, S., Laurent, S., Fontana, V., Ferro, P., Franceschini, M. C., Salvi, S., Varesano, S., Boccardo, S., Vigani, A., Morabito, A., et al. (2016) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-016-1844-3 · Cited by 47 · see citing works
Biomarkers and Immunotherapeutic Targets in Glioblastoma
Hung, A. L., Garzón-Muvdi, T., & Lim, M. K. (2017) · World Neurosurgery · doi:10.1016/j.wneu.2017.03.011 · Cited by 47 · see citing works
The immune checkpoints CTLA-4 and PD-L1 in carcinomas of the uterine cervix
Karpathiou, G., Chauleur, C., Mobarki, M., & Péoc’h, M. (2019) · Pathology - Research and Practice · doi:10.1016/j.prp.2019.152782 · Cited by 46 · see citing works
Deng, L., Győrffy, B., Na, F., Chen, B., Lan, J., Xue, J., Zhou, L., & Lü, Y. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000550 · Cited by 45 · see citing works
Abnormal alternative splicing promotes tumor resistance in targeted therapy and immunotherapy
Deng, K., Yao, J., Huang, J., Ding, Y., & Zuo, J. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101077 · Cited by 44 · see citing works
Noninvasive Imaging of Cancer Immunotherapy
Abousaway, O., Rakhshandehroo, T., den Abbeele, A. D. V., Kircher, M. F., & Rashidian, M. (2020) · Nanotheranostics · doi:10.7150/ntno.50860 · Cited by 43 · see citing works
Regulatory T cells and potential inmmunotherapeutic targets in lung cancer
Zhang, D., Chen, Z., Wang, D. C., & Wang, X. (2015) · Cancer and Metastasis Reviews · doi:10.1007/s10555-015-9566-0 · Cited by 42 · see citing works
Birtalan, E., Dános, K., Gurbi, B., Brauswetter, D., Halasz, J., Piurkó, V., Ács, B., Antal, B., Mihalyi, R., Pató, A., et al. (2017) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000590 · Cited by 41 · see citing works
Emerging Immunotherapy Approaches for Treating Prostate Cancer
Meng, L., Yang, Y., Mortazavi, A., & Zhang, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814347 · Cited by 41 · see citing works
de Vos, L., Grünwald, I., Bawden, E., Dietrich, J., Scheckenbach, K., Wiek, C., Zarbl, R., Bootz, F., Landsberg, J., & Dietrich, D. (2020) · Epigenetics · doi:10.1080/15592294.2020.1754675 · Cited by 40 · see citing works
Ariyarathna, H., Thomson, N. A., Aberdein, D., Perrott, M. R., & Munday, J. S. (2020) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2020.110142 · Cited by 39 · see citing works
Xiao, Y., Li, Z., Zhong, N., Cao, L., Liu, B., & Bu, L. (2023) · Translational Oncology · doi:10.1016/j.tranon.2023.101794 · Cited by 37 · see citing works
Antczak, A. J., Pastuszak‐Lewandoska, D., Górski, P., Domańska, D., Migdalska‐Sęk, M., Czarnecka, K. H., Nawrot, E., Kordiak, J., & Brzeziańska‐Lasota, E. (2013) · BioMed Research International · doi:10.1155/2013/576486 · Cited by 37 · see citing works
Szostak, B., Machaj, F., Rosik, J., & Pawlik, A. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2019.1559297 · Cited by 37 · see citing works
FDG PET/CT for Evaluation of Immunotherapy Response in Lung Cancer Patients
Leger, M. C., Routy, B., & Juneau, D. (2022) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2022.04.010 · Cited by 37 · see citing works
High CTLA-4 expression correlates with poor prognosis in thymoma patients
Santoni, G., Amantini, C., Morelli, M. B., Tomassoni, D., Santoni, M., Marinelli, O., Nabissi, M., Cardinali, C., Paolucci, V., Torniai, M., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24645 · Cited by 36 · see citing works
Grossi, F., Bello, M. G. D., Salvi, S., Puzone, R., Pfeffer, U., Fontana, V., Alama, A., Rijavec, E., Barletta, G., Genova, C., et al. (2015) · Disease Markers · doi:10.1155/2015/302649 · Cited by 34 · see citing works
Clinical Relevance of the serum CTLA-4 in Cats with Mammary Carcinoma
Urbano, A. C., Nascimento, C., Soares, M., Correia, J., & Ferreira, F. (2020) · Scientific Reports · doi:10.1038/s41598-020-60860-3 · Cited by 35 · see citing works
Lafuente-Sanchis, A., Zúñiga, Á., Estors, M., Hernández, N. J. M., Cremades, A., Cuenca, M., & Galbis, J. M. (2016) · Clinical Lung Cancer · doi:10.1016/j.cllc.2016.09.010 · Cited by 34 · see citing works
Disrupting cancer angiogenesis and immune checkpoint networks for improved tumor immunity
Anderson, T. S., McCormick, A. L., Piersall, S. L., Okpalanwaka, I. F., & Lowe, D. B. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.009 · Cited by 32 · see citing works
Clinical advances in EGFR-TKI combination therapy for EGFR-mutated NSCLC: a narrative review
Zhang, Q., Wang, R., & Xu, L. (2023) · Translational Cancer Research · doi:10.21037/tcr-23-956 · Cited by 31 · see citing works
Lan, G., Li, J., Wen, Q., Lin, L., Chen, L., Chen, L.-Y., & Chen, X. (2018) · Oncology Letters · doi:10.3892/ol.2018.7991 · Cited by 31 · see citing works
Zhang, S., Bai, W., Tong, X., Bu, P., Xu, J., & Xi, Y. (2018) · Oncology Letters · doi:10.3892/ol.2018.9682 · Cited by 29 · see citing works
Immune cell landscape in therapy-naïve squamous cell and adenocarcinomas of the lung
Brčić, L., Stanzer, S., Krenbek, D., Gruber-Moesenbacher, U., Absenger, G., Quehenberger, F., Valipour, A., Lindenmann, J., Stoeger, H., Effah, M. A., et al. (2018) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-018-2326-0 · Cited by 29 · see citing works
Pistillo, M. P., Carosio, R., Grillo, F., Fontana, V., Mastracci, L., Morabito, A., Banelli, B., Tanda, E. T., Cecchi, F., Dozin, B., et al. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108428 · Cited by 29 · see citing works
Wang, H., Sun, M., Guo, J., Ma, L., Jiang, H., Gu, L., Wen, H., Liao, S., Chen, J., Zeng, B., et al. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.03.007 · Cited by 27 · see citing works
Prevalence of DLL3, CTLA-4 and MSTN Expression in Patients with Small Cell Lung Cancer
Regzedmaa, O., Li, Y., Li, Y., Zhang, H., Wang, J., Gong, H., Yin, Y., Li, W., Liu, H., & Chen, J. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s216362 · Cited by 27 · see citing works
Krishnamurthy, N., Nishizaki, D., Lippman, S. M., Miyashita, H., Nesline, M., Pabla, S., Conroy, J. M., DePietro, P., Kato, S., & Kurzrock, R. (2024) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359231220510 · Cited by 27 · see citing works
Xiang, S., Li, S., & Xu, J. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70345 · Cited by 26 · see citing works
Lim, Y. J., Koh, J., Kim, K., Chie, E. K., Kim, S., Lee, K. B., Jang, J., Kim, S., Oh, D., & Bang, Y. (2017) · Targeted Oncology · doi:10.1007/s11523-016-0474-1 · Cited by 24 · see citing works
Targeting PD-1/PD-L1 in lung cancer: current perspectives
Rosell, R., González‐Cao, M., Karachaliou, N., Viteri, S., Espinosa, D. M., Teixidó, C., Ruiz, J. S., Molina‐Vila, M. Á., & Santarpía, M. (2015) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s55176 · Cited by 24 · see citing works
Feng, X.-Y., Wen, X.-Z., TAN, X.-J., Hou, J.-H., Ding, Y., Wang, K.-F., Dong, J., Zhou, Z.-W., Chen, Y., & Zhang, X.-S. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.2699 · Cited by 24 · see citing works
Role of Immunotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer
Rijavec, E., Genova, C., Alama, A., Barletta, G., Sini, C., Pronzato, P., Coco, S., Bello, M. G. D., Savarino, G., Truini, A., et al. (2013) · Future Oncology · doi:10.2217/fon.13.145 · Cited by 23 · see citing works
Bağbudar, S., Karanlik, H., Cabioglu, N., Bayram, A., Ibis, K., Aydin, E., Yavuz, E., & Onder, S. (2021) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000978 · Cited by 21 · see citing works
Clinical burden of immune checkpoint inhibitor-induced pneumonitis
Sakamoto, K., Fukihara, J., Morise, M., & Hashimoto, N. (2020) · Respiratory Investigation · doi:10.1016/j.resinv.2020.05.008 · Cited by 21 · see citing works
He, G., Liu, X., Pan, X., Ma, Y., & Liu, X. (2020) · Clinical & Translational Oncology · doi:10.1007/s12094-020-02387-7 · Cited by 20 · see citing works
Tumor‑infiltrating lymphocytes in primary tumors of colorectal cancer and their metastases
Jakubowska, K., Koda, M., Kisielewski, W., Kańczuga‐Koda, L., & FAMULSKI, W. (2019) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2019.8146 · Cited by 19 · see citing works
Immune Checkpoint Imaging in Oncology: A Game Changer Toward Personalized Immunotherapy?
Lütje, S., Feldmann, G., Essler, M., Brossart, P., & Bundschuh, R. A. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.237891 · Cited by 18 · see citing works
Usó, M., Lewintre, E. J., Fariñas, S. C., Blasco, A., del Olmo, E. G., Guijarro, R., Martorell, M., Camps, C., & Sirera, R. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1260214 · Cited by 18 · see citing works
Zhang, Y., Yang, S., Zhang, H., Gao, L., Gao, X., Liu, P., Yi, Z., Li, N., & Xu, Z. (2017) · Future Oncology · doi:10.2217/fon-2016-0437 · Cited by 16 · see citing works
(2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.1000-9604.2013.11.06 · Cited by 16 · see citing works
The Current State of Neoadjuvant Therapy in Resectable Advanced Stage Melanoma
Bushara, O., Tidwell, J. C., Wester, J. R., & Miura, J. T. (2023) · Cancers · doi:10.3390/cancers15133344 · Cited by 15 · see citing works
Current and Future Therapeutic Targets: A Review on Treating Head and Neck Squamous Cell Carcinoma
Madhukar, G., & Subbarao, N. (2020) · Current Cancer Drug Targets · doi:10.2174/1568009620666201229120332 · Cited by 15 · see citing works
Targeting the immune system to treat lung cancer: rationale and clinical experience
Guibert, N. M., Delaunay, M., & Mazières, J. (2015) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465815578349 · Cited by 14 · see citing works
Zhang, P., Bao, Z., Xu, L., Zhou, J., Lu, G., Yao, Y., Liu, R., Gao, Q., Shen, Y., & Zhou, J. (2017) · Oncotarget · doi:10.18632/oncotarget.19973 · Cited by 14 · see citing works
Lipid Metabolism and Immune Checkpoints
Liao, Q., Zhou, Y., Xia, L., & Cao, D. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-981-33-6785-2_12 · Cited by 14 · see citing works
Gardiner, R., Jahangeer, S. M., Forde, P. F., Ariffin, A. B., Bird, B., Soden, D. M., & Hinchion, J. (2015) · Cancer and Metastasis Reviews · doi:10.1007/s10555-015-9550-8 · Cited by 14 · see citing works
A molecular and immunohistochemical study of 37 cases of ovarian Sertoli–Leydig cell tumor
Němejcová, K., Hájková, N., Krkavcová, E., Bártů, M., Michálková, R., Šafanda, A., Švajdler, M., Shatokhina, T., Laco, J., Matěj, R., et al. (2024) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-024-03984-5 · Cited by 13 · see citing works
Qiang, H., Li, J., Chang, Q., Shen, Y., Qian, J., & Chu, T. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.835225 · Cited by 13 · see citing works
Kulbay, M., Tuli, N., Mazza, M., Jaffer, A., Juntipwong, S., Marcotte, E., Tanya, S. M., Nguyen, A. X.-L., Burnier, M. N., & Demirci, H. (2025) · Biomedicines · doi:10.3390/biomedicines13010108 · Cited by 12 · see citing works
Rijavec, E., Genova, C., Barletta, G., Burrafato, G., Biello, F., Bello, M. G. D., Coco, S., Truini, A., Alama, A., Boccardo, F., et al. (2014) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2014.907786 · Cited by 11 · see citing works
Kaneko, A., Kobayashi, N., Miura, K., Matsumoto, H., Somekawa, K., Hirose, T., Kajita, Y., Tanaka, A., Teranishi, S., Sairenji, Y., et al. (2024) · Thoracic Cancer · doi:10.1111/1759-7714.15304 · Cited by 10 · see citing works
Kujtan, L. A., Kancha, R. K., Gustafson, B., Douglass, L., Ward, C. R., Buzard, B., & Subramanian, J. (2022) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2022.2029414 · Cited by 10 · see citing works
An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers
Němejcová, K., Šafanda, A., Bártů, M., Michálková, R., Švajdler, M., Shatokhina, T., Laco, J., Matěj, R., Méhes, G., Drozenová, J., et al. (2024) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-024-03854-0 · Cited by 9 · see citing works
Extracellular Vesicle-Based Strategies for Tumor Immunotherapy
Jiramonai, L., Liang, X.-J., & Zhu, M. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17020257 · Cited by 9 · see citing works
Is there a room for immune checkpoint inhibitors in early stage non-small cell lung cancer?
Gobbini, É., & Levra, M. G. (2018) · Journal of Thoracic Disease · doi:10.21037/jtd.2018.01.81 · Cited by 9 · see citing works
Mohamed, A. S. E. D., El-Rebey, H. S., Aboelnasr, L. S., & Abdou, A. G. (2021) · ecancermedicalscience · doi:10.3332/ecancer.2021.1323 · Cited by 8 · see citing works
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
