Abstract
| Original language | English |
|---|---|
| Journal | Frontiers in Immunology |
| Volume | 8 |
| Issue number | APR |
| DOIs | |
| Publication status | Published - 2017 |
Keywords
- Best overall response
- CTLA-4 variants
- Ipilimumab
- Melanoma
- Overall survival
- Predictive/prognostic factor
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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. / Queirolo, P.; Dozin, B.; Morabito, A.; Banelli, B.; Piccioli, P.; Fava, C.; Leo, C.; Carosio, R.; Laurent, S.; Fontana, V.; Ferrucci, P.F.; Martinoli, C.; Cocorocchio, E.; Battaglia, A.; Ascierto, P.A.; Capone, M.; Simeone, E.; De Galitiis, F.; Pagani, E.; Cappellini, G.C.A.; Marchetti, P.; Guida, M.; Tommasi, S.; Mandalà, M.; Merelli, B.; Quaglino, P.; Fava, P.; Guidoboni, M.; Romani, M.; Spagnolo, F.; Pistillo, M.P.
In: Frontiers in Immunology, Vol. 8, No. APR, 2017.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - 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
AU - Queirolo, P.
AU - Dozin, B.
AU - Morabito, A.
AU - Banelli, B.
AU - Piccioli, P.
AU - Fava, C.
AU - Leo, C.
AU - Carosio, R.
AU - Laurent, S.
AU - Fontana, V.
AU - Ferrucci, P.F.
AU - Martinoli, C.
AU - Cocorocchio, E.
AU - Battaglia, A.
AU - Ascierto, P.A.
AU - Capone, M.
AU - Simeone, E.
AU - De Galitiis, F.
AU - Pagani, E.
AU - Cappellini, G.C.A.
AU - Marchetti, P.
AU - Guida, M.
AU - Tommasi, S.
AU - Mandalà, M.
AU - Merelli, B.
AU - Quaglino, P.
AU - Fava, P.
AU - Guidoboni, M.
AU - Romani, M.
AU - Spagnolo, F.
AU - Pistillo, M.P.
N1 - Export Date: 14 July 2017 Correspondence Address: Pistillo, M.P.; Unit of Tumor Epigenetics, IRCCS AOU San Martino-IST-Istituto Nazionale per la Ricerca sul CancroItaly; email: mariapia.pistillo@hsanmartino.it References: Brunner, M.C., Chambers, C.A., Chan, F.K., Hanke, J., Winoto, A., Allison, J.P., CTLA-4-mediated inhibition of early events of T cell proliferation (1999) J Immunol, 162, pp. 5813-5820; Walker, L.S., Sansom, D.M., The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses (2011) Nat Rev Immunol, 11, pp. 852-863; Peggs, K.S., Quezada, S.A., Korman, A.J., Allison, J.P., Principles and use of anti-CTLA-4 antibody in human cancer immunotherapy (2006) Curr Opin Immunol, 18, pp. 206-231; Tarhini, A.A., Edington, H., Butterfield, L.H., Lin, Y., Shuai, Y., Tawbi, H., Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab (2014) PLoS One, 9; Hodi, F.S., O'Day, S.J., McDermott, D.F., Weber, R.W., Sosman, J.A., Haanen, J.B., Improved survival with ipilimumab in patients with metastatic melanoma (2010) N Engl J Med, 363, pp. 711-723; Robert, C., Thomas, L., Bondarenko, I., O'Day, S., Weber, J., Garbe, C., Ipilimumab plus dacarbazine for previously untreated metastatic melanoma (2011) N Engl J Med, 364, pp. 2517-2526; Schadendorf, D., Hodi, F.S., Robert, C., Weber, J.S., Margolin, K., Hamid, O., Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma (2015) J Clin Oncol, 33, pp. 1889-1894; Martens, A., Wistuba-Hamprecht, K., Geukes Foppen, M., Yuan, J., Postow, M.A., Wong, P., Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab (2016) Clin Cancer Res, 22, pp. 2908-2918; Ferrucci, P.F., Ascierto, P.A., Pigozzo, J., Del Vecchio, M., Maio, M., Antonini Cappellini, G.C., Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab (2016) Ann Oncol, 27, pp. 732-738; Ji, R.R., Chasalow, S.D., Wang, L., Hamid, O., Schmidt, H., Cogswell, J., An immune-active tumor microenvironment favors clinical response to ipilimumab (2012) Cancer Immunol Immunother, 61, pp. 1019-1031; Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J.M., Desrichard, A., Genetic basis for clinical response to CTLA-4 blockade in melanoma (2014) N Engl J Med, 371, pp. 2189-2199; Blank, C.U., Haanen, J.B., Ribas, A., Schumacher, T.N., CANCER IMMUNOLOGY. The "cancer immunogram" (2016) Science, 352, pp. 658-660; Topalian, S.L., Taube, J.M., Anders, R.A., Pardoll, D.M., Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy (2016) Nat Rev Cancer, 16, pp. 275-287; Ueda, H., Howson, J.M., Esposito, L., Heward, J., Snook, H., Chamberlain, G., Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease (2003) Nature, 423, pp. 506-511; Wang, X.B., Zhao, X., Giscombe, R., Lefvert, A.K., A CTLA-4 gene polymorphism at position-318 in the promoter region affects the expression of protein (2002) Genes Immun, 3, pp. 233-234; Chistiakov, D.A., Savost'anov, K.V., Turakulov, R.I., Efremov, I.A., Demurov, L.M., Genetic analysis and functional evaluation of the C/T(-318) and A/G(-1661) polymorphisms of the CTLA-4 gene in patients affected with Graves' disease (2006) Clin Immunol, 118, pp. 233-242; Anjos, S., Nguyen, A., Ounissi-Benkalha, H., Tessier, M.C., Polychronakos, C., A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele (2002) J Biol Chem, 277, pp. 46478-46486; Sun, T., Zhou, Y., Yang, M., Hu, Z., Tan, W., Han, X., Functional genetic variations in cytotoxic T-lymphocyte antigen 4 and susceptibility to multiple types of cancer (2008) Cancer Res, 68, pp. 7025-7034; Breunis, W.B., Tarazona-Santos, E., Chen, R., Kiley, M., Rosenberg, S.A., Chanock, S.J., Influence of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) common polymorphisms on outcome in treatment of melanoma patients with CTLA-4 blockade (2008) J Immunother, 31, pp. 586-590; Queirolo, P., Morabito, A., Laurent, S., Lastraioli, S., Piccioli, P., Ascierto, P.A., Association of CTLA-4 polymorphisms with improved overall survival in melanoma patients treated with CTLA-4 blockade: a pilot study (2013) Cancer Invest, 31, pp. 336-345; Ascierto, P.A., Simeone, E., Sileni, V.C., Pigozzo, J., Maio, M., Altomonte, M., Clinical experience with ipilimumab 3 mg/kg: real-world efficacy and safety data from an expanded access programme cohort (2014) J Transl Med, 12, p. 116; Wolchok, J.D., Hoos, A., O'Day, S., Weber, J.S., Hamid, O., Lebbé, C., Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria (2009) Clin Cancer Res, 15, pp. 7412-7420; Banelli, B., Morabito, A., Laurent, S., Piccioli, P., Dozin, B., Ghio, M., A novel multiplex pyrosequencing assay for genotyping functionally relevant CTLA-4 polymorphisms: potential applications in autoimmunity and cancer (2014) Hum Immunol, 75, pp. 730-739; Piccioli, P., Balbi, G., Serra, M., Morabito, A., Lamparelli, T., Gobbi, M., CTLA-4 +49A>G polymorphism of recipients of HLA-matched sibling allogeneic stem cell transplantation is associated with survival and relapse incidence (2010) Ann Hematol, 89, pp. 613-618; Gogas, H., Dafni, U., Koon, H., Spyropoulou-Vlachou, M., Metaxas, Y., Buchbinder, E., Evaluation of six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon therapy in the He13A/98 multicenter trial (2010) J Transl Med, 8, p. 108; Hosmer, D.W., Lemeshow, S., (2000) Applied Logistic Regression, , 2nd ed. New York, NY: John Wiley and Sons Inc; Palacios, R., Comas, D., Elorza, J., Villoslada, P., Genomic regulation of CTLA4 and multiple sclerosis (2008) J Neuroimmunol, 203, pp. 108-115; Atabani, S.F., Thio, C.L., Divanovic, S., Trompette, A., Belkaid, Y., Thomas, D.L., Association of CTLA4 polymorphism with regulatory T cell frequency (2005) Eur J Immunol, 35, pp. 2157-2162; Laurent, S., Queirolo, P., Boero, S., Salvi, S., Piccioli, P., Boccardo, S., The engagement of CTLA-4 on primary melanoma cell lines induces antibody-dependent cellular cytotoxicity and TNF-a production (2013) J Transl Med, 11, p. 108; Romano, E., Kusio-Kobialka, M., Foukas, P.G., Baumgaertner, P., Meyer, C., Ballabeni, P., Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients (2015) Proc Natl Acad Sci U S A, 112, pp. 6140-6145; Eggermont, A.M., Chiarion-Sileni, V., Grob, J.J., Dummer, R., Wolchok, J.D., Schmidt, H., Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial (2015) Lancet Oncol, 16, pp. 522-530; Queirolo, P., Picasso, V., Spagnolo, F., Combined BRAF and MEK inhibition for the treatment of BRAF-mutated metastatic melanoma (2015) Cancer Treat Rev, 41, pp. 519-526; Robert, C., Schachter, J., Long, G.V., Arance, A., Grob, J.J., Mortier, L., Pembrolizumab versus ipilimumab in advanced melanoma (2015) N Engl J Med, 372, pp. 2521-2532; Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J.J., Cowey, C.L., Lao, C.D., Combined nivolumab and ipilimumab or monotherapy in untreated melanoma (2015) N Engl J Med, 373, pp. 23-34
PY - 2017
Y1 - 2017
N2 - 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. © 2017 Queirolo, Dozin, Morabito, Banelli, Piccioli, Fava, Leo, Carosio, Laurent, Fontana, Ferrucci, Martinoli, Cocorocchio, Battaglia, Ascierto, Capone, Simeone, De Galitiis, Pagani, Antonini Cappellini, Marchetti, Guida, Tommasi, Mandalà, Merelli, Quaglino, Fava, Guidoboni, Romani, Spagnolo and Pistillo.
AB - 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. © 2017 Queirolo, Dozin, Morabito, Banelli, Piccioli, Fava, Leo, Carosio, Laurent, Fontana, Ferrucci, Martinoli, Cocorocchio, Battaglia, Ascierto, Capone, Simeone, De Galitiis, Pagani, Antonini Cappellini, Marchetti, Guida, Tommasi, Mandalà, Merelli, Quaglino, Fava, Guidoboni, Romani, Spagnolo and Pistillo.
KW - Best overall response
KW - CTLA-4 variants
KW - Ipilimumab
KW - Melanoma
KW - Overall survival
KW - Predictive/prognostic factor
U2 - 10.3389/fimmu.2017.00386
DO - 10.3389/fimmu.2017.00386
M3 - Article
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - APR
ER -