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

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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.

TidsskriftFrontiers in Genetics
Antal sider13
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
Funding was provided by Novo Nordisk Foundation (grant no. 0052931) and European Research Council (grant no. 677268 ERC StG nextDART). The Danish Cancer Society (grant number: R149-444 A10123) and Preben&Anna Simonsens Fund (grant number: 021892-0009s).

Publisher Copyright:
Copyright © 2023 Borch, Bjerregaard, Araujo Barbosa de Lima, Østrup, Yde, Eklund, Mau-Sørensen, Barra, Svane, Nielsen, Funt, Lassen and Hadrup.

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