547 FOXD1 is overexpressed in melanoma but not in melanocytic nevi, and associated with melanoma cells proliferation

Abstract

Immune checkpoint inhibitors blocking the interaction between PD-1 and PD-L1 are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been still controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immunerelated genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment. We found that, in addition to the PD-L1 (P ¼ 0.03), expression levels of PD-1 ligand-2 (PD-L2), granzyme A (GZMA) and human leukocyte antigen-A (HLA-A) in the pre-treatment tumors were significantly higher (P ¼ 0.04, P ¼ 0.01 and P ¼ 0.006, respectively) in responders than in non-responders. With nivolumab treatment, tumors in responders exhibited a substantial increase of CD8, GZMA and perforin 1 (PRF1) expression levels as well as increased ratio of TBX21/GATA3, suggesting dominancy of Th1 response. The scoring system using three possible biomarkers