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

Journal for Immunotherapy of Cancer
Yong QinSapna P Patel

Abstract

To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies. Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set. Both primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absen...Continue Reading

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Citations

Mar 3, 2021·Expert Opinion on Investigational Drugs·Christos MasaoutisStamatios Theocharis
Mar 26, 2021·Clinical Epigenetics·Iris LodewijkJesús M Paramio
May 1, 2021·Cancers·Mariarosaria MarsegliaMichela Croce
May 6, 2021·Journal of Experimental & Clinical Cancer Research : CR·Anna TosiAntonio Rosato
Jul 2, 2021·Journal of Immunology Research·Mieszko LachotaRadoslaw Zagozdzon

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Methods Mentioned

BETA
Biopsy
RNAseq
RNA-seq

Software Mentioned

Ingenuity Pathway Analysis ( IPA )
Ingenuity Pathways Analysis ( IPA )
IPA
GraphPad Prism
NanoString
NanoString nCounter
nCounter PanCancer Immune Profiling codeset NanoString
Aperio

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