TY - JOUR

T1 - Neoepitope load, T cell signatures and PD-L2 as combined biomarker strategy for response to checkpoint inhibition immunotherapy

AU - Borch, Annie

AU - Bjerregaard, Anne Mette

AU - Araujo Barbosa de Lima, Vinicius

AU - Østrup, Olga

AU - Yde, Christina Westmose

AU - Eklund, Aron Charles

AU - Mau-Sørensen, Morten

AU - Barra, Carolina

AU - Svane, Inge Marie

AU - Nielsen, Finn Cilius

AU - Funt, Samuel A.

AU - Lassen, Ulrik

AU - Hadrup, Sine Reker

N1 - Publisher Copyright: Copyright © 2023 Borch, Bjerregaard, Araujo Barbosa de Lima, Østrup, Yde, Eklund, Mau-Sørensen, Barra, Svane, Nielsen, Funt, Lassen and Hadrup.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - biomarker

KW - immune checkpoint inhibition

KW - immunotherapy

KW - neoepitopes

KW - programmed cell death 1 ligand 2

KW - T cell signatures

KW - tumor mutational burden

U2 - 10.3389/fgene.2023.1058605

DO - 10.3389/fgene.2023.1058605

M3 - Journal article

C2 - 37035751

AN - SCOPUS:85151945928

VL - 14

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

M1 - 1058605

ER -