Unknown

Dataset Information

0

Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy.


ABSTRACT: Anti-PD-1 therapy yields objective clinical responses in 30-40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFN?-stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of 'PD-1 signalling', 'allograft rejection' and 'T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1-treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4(+) and CD8(+) tumour infiltrate. MHC-II(+) tumours can be identified by melanoma-specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection.

SUBMITTER: Johnson DB 

PROVIDER: S-EPMC4740184 | BioStudies | 2016-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5975601 | BioStudies
2019-01-01 | S-EPMC6343795 | BioStudies
2018-01-01 | S-EPMC6095740 | BioStudies
2017-01-01 | S-EPMC5741628 | BioStudies
2020-01-01 | S-EPMC7171183 | BioStudies
2017-01-01 | S-EPMC5875182 | BioStudies
2019-01-01 | S-EPMC6461865 | BioStudies
2017-01-01 | S-EPMC5282822 | BioStudies
2015-01-01 | S-EPMC4558214 | BioStudies
2015-01-01 | S-EPMC6094609 | BioStudies