Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10582
Keywords
-
Categories
Funding
- Vanderbilt Ingram Cancer Center [P30 CA68485]
- Vanderbilt Digestive Disease Research Center [DK058404]
- Damon Runyon Clinical Investigator Award
- LUNGevity Career Development Award [T32CA009592, R00CA143231-03]
- [4R00CA181491]
- [K12CA0906525]
- [5R01CA121210-07]
- [5P01CA129243-06]
- NATIONAL CANCER INSTITUTE [R01CA116021, P30CA068485, R01CA034590, R00CA143231, P01CA129243, F31CA199993, R01CA121210, T32CA009592, R00CA181491] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK058404] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R25GM062459] Funding Source: NIH RePORTER
- Veterans Affairs [I01BX002301] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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 gamma-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available