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

Document Type

Article

Publication Date

10-1-2018

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 datasets1–6 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.

Identifier

85052285340 (Scopus)

Publication Title

Nature Medicine

External Full Text Location

https://doi.org/10.1038/s41591-018-0157-9

e-ISSN

1546170X

ISSN

10788956

PubMed ID

30127394

First Page

1545

Last Page

1549

Issue

10

Volume

24

Grant

41/11

Fund Ref

National Institutes of Health

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