Genetic aberrations in the CDK4 pathway are associated with innate resistance to PD-1 blockade in Chinese patients with non-cutaneous melanoma

Yan Kong, Jiayi Yu, Junya Yan, Qian Guo, Zhihong Chi, Bixia Tang, Bin Zheng, Jinyu Yu, Ting Yin, Zhiyuan Cheng, Xiaowei Wu, Huan Yu (+13 others)
2019 Clinical Cancer Research  
PD-1 checkpoint blockade immunotherapy induces long and durable response in patients with advanced melanoma. However, only a subset of patients with melanoma benefit from this approach. The mechanism triggering the innate resistance of anti-PD-1 therapy remains unclear.Experimental Design: Whole-exome sequencing (WES) and RNA sequencing (RNA-Seq) analyses were performed in a training cohort (n = 31) using baseline tumor biopsies of patients with advanced melanoma treated with the anti-PD-1
more » ... ody. Copy-number variations (CNVs) for the genes CDK4, CCND1, and CDKN2A were assayed using a TaqMan copy-number assay in a validation cohort (n = 85). The effect of CDK4/6 inhibitors combined with anti-PD-1 antibody monotherapy was evaluated in PD-1-humanized mouse (C57BL/6-hPD-1) and humanized immune system (HIS) patient-derived xenograft (PDX) models.
doi:10.1158/1078-0432.ccr-19-0475 pmid:31375512 fatcat:qtt7ejpuxng5nl2kuprds2hiei