Neoepitope load, T cell signatures and PD-L2 as combined biomarker strategy for response to checkpoint inhibition immunotherapy

Annie Borch, Anne-Mette Bjerregaard, Vinicius Araujo Barbosa de Lima, Olga Østrup, Christina Westmose Yde, Aron Charles Eklund, Morten Mau-Sørensen, Carolina Barra, Inge Marie Svane, Finn Cilius Nielsen, Samuel A Funt, Ulrik Lassen*, Sine Reker Hadrup*

*Corresponding author for this work

Abstract

Immune checkpoint inhibition for the treatment of cancer has provided a breakthrough in oncology, and several new checkpoint inhibition pathways are currently being investigated regarding their potential to provide additional clinical benefit. However, only a fraction of patients respond to such treatment modalities, and there is an urgent need to identify biomarkers to rationally select patients that will benefit from treatment. In this study, we explore different tumor associated characteristics for their association with favorable clinical outcome in a diverse cohort of cancer patients treated with checkpoint inhibitors. We studied 29 patients in a basket trial comprising 12 different tumor types, treated with 10 different checkpoint inhibition regimens. Our analysis revealed that even across this diverse cohort, patients achieving clinical benefit had significantly higher neoepitope load, higher expression of T cell signatures, and higher PD-L2 expression, which also correlated with improved progression-free and overall survival. Importantly, the combination of biomarkers serves as a better predictor than each of the biomarkers alone. Basket trials are frequently used in modern immunotherapy trial design, and here we identify a set of biomarkers of potential relevance across multiple cancer types, allowing for the selection of patients that most likely will benefit from immune checkpoint inhibition.

Original languageEnglish
Article number1058605
JournalFrontiers in genetics
Volume14
Pages (from-to)1058605
ISSN1664-8021
DOIs
Publication statusPublished - 2023

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