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Updated: Mar 26, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1
Douglas B Johnson1, Monica V Estrada2, Roberto Salgado3
1Department of Medicine, Vanderbilt University, Nashville, 37232 Tennessee, USA.
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 IFNγ-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.
Insights
MHC-II expression in melanoma predicts response to anti-PD-1 therapy, offering a biomarker for improved patient selection. This finding enhances understanding of immune checkpoint inhibitor efficacy in advanced melanoma.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Anti-PD-1 therapy shows limited response rates in advanced melanoma, necessitating predictive biomarkers.
- Tumor antigen presentation via MHC-I and MHC-II is crucial for anti-PD-1 efficacy.
Purpose of the Study:
- To investigate the role of MHC-I and MHC-II expression as predictive biomarkers for anti-PD-1 therapy response in melanoma.
- To identify melanoma subsets with specific MHC expression patterns and their association with immune signaling pathways.
Main Methods:
- Analysis of MHC-I/II expression across 60 melanoma cell lines.
- Pathway analysis of MHC-II positive (MHC-II(+)) cell lines.
- Validation in two independent patient cohorts treated with anti-PD-1 therapy.
- Immunohistochemistry for HLA-DR expression.
Main Results:
- MHC-II expression was bimodal in melanoma cell lines, with a subset expressing MHC-II constitutively or upon IFNγ stimulation.
- MHC-II(+) cell lines exhibited enriched signatures for PD-1 signaling, allograft rejection, and T-cell receptor signaling.
- MHC-II positivity in patients correlated with improved therapeutic response, progression-free survival, overall survival, and increased CD4(+)/CD8(+) tumor infiltrate.
Conclusions:
- MHC-II expression is a potential predictive biomarker for anti-PD-1 therapy in melanoma.
- Immunohistochemical detection of HLA-DR can identify MHC-II(+) tumors for improved patient selection.
- MHC-II expression is linked to enhanced anti-tumor immune responses relevant to PD-1 blockade.
