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Article: Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma

TitleRobust prediction of response to immune checkpoint blockade therapy in metastatic melanoma
Authors
Issue Date2018
Citation
Nature Medicine, 2018, v. 24, n. 10, p. 1545-1549 How to Cite?
AbstractImmune checkpoint blockade (ICB) therapy provides remarkable clinical gains and has been very successful in treatment of melanoma. However, only a subset of patients with advanced tumors currently benefit from ICB therapies, which at times incur considerable side effects and costs. Constructing predictors of patient response has remained a serious challenge because of the complexity of the immune response and the shortage of large cohorts of ICB-treated patients that include both ‘omics’ and response data. Here we build immuno-predictive score (IMPRES), a predictor of ICB response in melanoma which encompasses 15 pairwise transcriptomics relations between immune checkpoint genes. It is based on two key conjectures: (i) immune mechanisms underlying spontaneous regression in neuroblastoma can predict melanoma response to ICB, and (ii) key immune interactions can be captured via specific pairwise relations of the expression of immune checkpoint genes. IMPRES is validated on nine published datasets1–6 and on a newly generated dataset with 31 patients treated with anti-PD-1 and 10 with anti-CTLA-4, spanning 297 samples in total. It achieves an overall accuracy of AUC = 0.83, outperforming existing predictors and capturing almost all true responders while misclassifying less than half of the nonresponders. Future studies are warranted to determine the value of the approach presented here in other cancer types.
Persistent Identifierhttp://hdl.handle.net/10722/318726
ISSN
2023 Impact Factor: 58.7
2023 SCImago Journal Rankings: 19.045
PubMed Central ID
ISI Accession Number ID
Errata

 

DC FieldValueLanguage
dc.contributor.authorAuslander, Noam-
dc.contributor.authorZhang, Gao-
dc.contributor.authorLee, Joo Sang-
dc.contributor.authorFrederick, Dennie T.-
dc.contributor.authorMiao, Benchun-
dc.contributor.authorMoll, Tabea-
dc.contributor.authorTian, Tian-
dc.contributor.authorWei, Zhi-
dc.contributor.authorMadan, Sanna-
dc.contributor.authorSullivan, Ryan J.-
dc.contributor.authorBoland, Genevieve-
dc.contributor.authorFlaherty, Keith-
dc.contributor.authorHerlyn, Meenhard-
dc.contributor.authorRuppin, Eytan-
dc.date.accessioned2022-10-11T12:24:25Z-
dc.date.available2022-10-11T12:24:25Z-
dc.date.issued2018-
dc.identifier.citationNature Medicine, 2018, v. 24, n. 10, p. 1545-1549-
dc.identifier.issn1078-8956-
dc.identifier.urihttp://hdl.handle.net/10722/318726-
dc.description.abstractImmune checkpoint blockade (ICB) therapy provides remarkable clinical gains and has been very successful in treatment of melanoma. However, only a subset of patients with advanced tumors currently benefit from ICB therapies, which at times incur considerable side effects and costs. Constructing predictors of patient response has remained a serious challenge because of the complexity of the immune response and the shortage of large cohorts of ICB-treated patients that include both ‘omics’ and response data. Here we build immuno-predictive score (IMPRES), a predictor of ICB response in melanoma which encompasses 15 pairwise transcriptomics relations between immune checkpoint genes. It is based on two key conjectures: (i) immune mechanisms underlying spontaneous regression in neuroblastoma can predict melanoma response to ICB, and (ii) key immune interactions can be captured via specific pairwise relations of the expression of immune checkpoint genes. IMPRES is validated on nine published datasets1–6 and on a newly generated dataset with 31 patients treated with anti-PD-1 and 10 with anti-CTLA-4, spanning 297 samples in total. It achieves an overall accuracy of AUC = 0.83, outperforming existing predictors and capturing almost all true responders while misclassifying less than half of the nonresponders. Future studies are warranted to determine the value of the approach presented here in other cancer types.-
dc.languageeng-
dc.relation.ispartofNature Medicine-
dc.titleRobust prediction of response to immune checkpoint blockade therapy in metastatic melanoma-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41591-018-0157-9-
dc.identifier.pmid30127394-
dc.identifier.pmcidPMC6693632-
dc.identifier.scopuseid_2-s2.0-85052285340-
dc.identifier.volume24-
dc.identifier.issue10-
dc.identifier.spage1545-
dc.identifier.epage1549-
dc.identifier.eissn1546-170X-
dc.identifier.isiWOS:000446577900017-
dc.relation.erratumdoi:10.1038/s41591-018-0247-8-
dc.relation.erratumeid:eid_2-s2.0-85055272306-

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