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Keratinocyte differentiation antigen-specific T cells in immune checkpoint inhibitor-treated NSCLC patients are associated with improved survival

Journal Paper/Review - Nov 27, 2021

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Berner F, Niederer R, Luimstra J, Pop O, Jochum A, Purde M, Hasan Ali O, Bomze D, Bauer J, Freudenmann L, Marcu A, Wolfschmitt E, Haen S, Gross T, Dubbelaar M, Abdou M, Baumgaertner P, Appenzeller C, Cicin-Sain C, Lenz T, Speiser D, Ludewig B, Driessen C, Jörger M, Früh M, Jochum W, Cozzio A, Rammensee H, Walz J, Neefjes J, Flatz L. Keratinocyte differentiation antigen-specific T cells in immune checkpoint inhibitor-treated NSCLC patients are associated with improved survival. Oncoimmunology 2021; 10:2006893.
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Journal Paper/Review (English)
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Oncoimmunology 2021; 10
Publication Date
Nov 27, 2021
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2162-402X
Pages
2006893
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Immune checkpoint inhibitors (ICIs) have improved the survival of patients with non-small cell lung cancer (NSCLC) by reinvigorating tumor-specific T cell responses. However, the specificity of such T cells and the human leukocyte antigen (HLA)-associated epitopes recognized, remain elusive. In this study, we identified NSCLC T cell epitopes of recently described NSCLC-associated antigens, termed keratinocyte differentiation antigens. Epitopes of these antigens were presented by HLA-A 03:01 and HLA-C 04:01 and were associated with responses to ICI therapy. Patients with CD8 T cell responses to these epitopes had improved overall and progression-free survival. T cells specific for such epitopes could eliminate HLA class I-matched NSCLC cells and were enriched in patient lung tumors. The identification of novel lung cancer HLA-associated epitopes that correlate with improved ICI-dependent treatment outcomes suggests that keratinocyte-specific proteins are important tumor-associated antigens in NSCLC. These findings improve our understanding of the mechanisms of ICI therapy and may help support the development of vaccination strategies to improve ICI-based treatment of these tumors.