IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma
| العنوان: | IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma |
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| المؤلفون: | Irene L.M. Reijers, Disha Rao, Judith M. Versluis, Alexander M. Menzies, Petros Dimitriadis, Michel W. Wouters, Andrew J. Spillane, Willem M.C. Klop, Annegien Broeks, Linda J.W. Bosch, Marta Lopez-Yurda, Winan J. van Houdt, Robert V. Rawson, Lindsay G. Grijpink-Ongering, Maria Gonzalez, Sten Cornelissen, Jasper Bouwman, Joyce Sanders, Elsemieke Plasmeijer, Yannick S. Elshot, Richard A. Scolyer, Bart A. van de Wiel, Daniel S. Peeper, Alexander C.J. van Akkooi, Georgina V. Long, Christian U. Blank |
| المساهمون: | Oral and Maxillofacial Surgery, Dermatology, Graduate School, AII - Infectious diseases, AII - Inflammatory diseases, CCA - Cancer Treatment and Quality of Life |
| المصدر: | Reijers, I L M, Rao, D, Versluis, J M, Menzies, A M, Dimitriadis, P, Wouters, M W, Spillane, A J, Klop, W M C, Broeks, A, Bosch, L J W, Lopez-Yurda, M, van Houdt, W J, Rawson, R V, Grijpink-Ongering, L G, Gonzalez, M, Cornelissen, S, Bouwman, J, Sanders, J, Plasmeijer, E, Elshot, Y S, Scolyer, R A, van de Wiel, B A, Peeper, D S, van Akkooi, A C J, Long, G V & Blank, C U 2023, ' IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma ', Journal of Experimental Medicine, vol. 220, no. 5, e20221952 . https://doi.org/10.1084/jem.20221952Test Journal of experimental medicine, 220(5):e20221952. Rockefeller University Press Journal of Experimental Medicine, 220(5):e20221952. Rockefeller University Press |
| بيانات النشر: | Rockefeller University Press, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial. Patients with stage III melanoma and high intra-tumoral IFN-γ scores were randomized to neoadjuvant nivolumab or nivolumab + domatinostat, while patients with low IFN-γ scores received nivolumab + domatinostat or ipilimumab + nivolumab + domatinostat. Domatinostat addition to neoadjuvant nivolumab ± ipilimumab did not delay surgery but induced unexpected severe skin toxicity, hampering domatinostat dose escalation. At studied dose levels, domatinostat addition did not increase treatment efficacy. The baseline IFN-γ score adequately differentiated patients who were likely to benefit from nivolumab alone versus patients who require other therapies. |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::17999c5aac89a5332bee79a05cb4e596Test https://doi.org/10.1084/jem.20221952Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....17999c5aac89a5332bee79a05cb4e596 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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