Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy

• DOI: 10.1136/jitc-2020-000960
• Publication Date: 2020-11-17T21:46:17Z
• Authors: Yong Qin; Kathryn Bollin; Mariana Petaccia ...; Fernando Carapeto; Kevin B Kim; Jason Roszik; Khalida M Wani; Alexandre Reuben; Sujan T Reddy; Michelle D Williams; Michael T Tetzlaff; Wei-Lien Wang; Dan S Gombos; Bita Esmaeli; Alexander J Lazar; Patrick Hwu; Sapna P Patel
• Keywords: Profiling (computer programming); Signature (topology)

To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. understand the role of immune infiltrates genesis, metastasis, and response treatment for UM, we systematically characterized profiles UM primary tumors, as well samples from patients treated with immunotherapies. Relevant markers (CD3, CD8, FoxP3, CD68, PD-1, PD-L1) were analyzed by immunohistochemistry on 27 31 tumors 47 UM. Immune gene expression profiling was conducted NanoString analysis pre-treatment post-treatment (n=6) receiving checkpoint blockade or 4-1BB OX40 dual costimulation. The signature responding immunotherapy further Ingenuity Pathways Analysis validated Cancer Genome Atlas data set. Both showed detectable infiltrating lymphocytes. Compared treatment-naïve significantly higher levels CD3+, CD8+, FoxP3+ T cells, CD68+ macrophages. Notably, PD-1+ PD-L1+ tumor cells low absent tumors. No organ-specific differences seen infiltrates. Our revealed significant a set between responders non-responders. A group genes relevant interferon-γ differentially up-expressed responders. Among these genes, suppressor cytokine signaling 1 identified marker potentially contributing immunotherapy. panel that encoded pro-inflammatory cytokines molecules expressed non-responders compared study provides critical insight into which suggests baseline predictive resistance