Novel Anti-PD1 Predictive Signature and Functional Dendritic-Cell Biomarkers in Melanoma Identified with Systems Immunology
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Despite the success of anti-PD1 immunotherapy in melanoma, identifying biomarkers for response prediction and rational treatment combinations remains a major challenge. Effective dendritic cell (DC):CD8+ T cell crosstalk in the tumor microenvironment enhances anti-PD1 responses; however, no predictive signatures reflect this interaction. To address this, we developed a systems immunology approach based on DC:CD8+ T cell crosstalk reference biomarkers CD74 and CD8A, leading to the discovery of a 15-gene immune signature called PRIME, incorporated into a logistic regression framework for anti-PD1 response prediction in melanoma. PRIME outperforms previous signatures, especially in tumors with high CD8+ T cells, reflecting a functional immune response. Integrating clinical, molecular, spatial, and single-cell profiling identified SLAMF7 and TYMP as new functional biomarker candidates in DCs. Mechanistic studies revealed that these biomarkers regulate antigen processing and presentation in DCs. Our study demonstrates a new strategy for predicting anti-PD1 responses in melanoma, revealing biomarkers with functional roles that may inform future therapeutic development.
