Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma
Top Cited Papers
- 20 August 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 24 (10), 1545-1549
- https://doi.org/10.1038/s41591-018-0157-9
Abstract
Immune 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 datasets1,2,3,4,5,6 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.Keywords
This publication has 30 references indexed in Scilit:
- Tumor and Microenvironment Evolution during Immunotherapy with NivolumabCell, 2017
- Immune-Related Gene Expression Profiling After PD-1 Blockade in Non–Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and MelanomaCancer Research, 2017
- Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint BlockadeCancer Discovery, 2016
- Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic MelanomaCell, 2016
- Genomic correlates of response to CTLA-4 blockade in metastatic melanomaScience, 2015
- Mechanisms of neuroblastoma regressionNature Reviews Clinical Oncology, 2014
- Spontaneous regression of metastatic melanoma – Clinical evidence of the abscopal effectEuropean Journal of Surgical Oncology, 2014
- The Cancer Genome Atlas Pan-Cancer analysis projectNature Genetics, 2013
- Spontaneous regression of metastases from melanoma: review of the literatureMelanoma Research, 2009
- Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma.Journal of Clinical Oncology, 1987