Keratinocyte differentiation antigen-specific T cells in immune checkpoint inhibitor-treated NSCLC patients are associated with improved survival
Journal Paper/Review - Nov 27, 2021
Berner Fiamma, Appenzeller Christina, Cicin-Sain Caroline, Lenz Tobias, Speiser Daniel E, Ludewig Burkhard, Driessen Christoph, Jörger Markus, Früh Martin, Jochum Wolfram, Cozzio Antonio, Rammensee Hans-Georg, Walz Juliane, Neefjes Jacques, Baumgaertner Petra, Abdou Marie-Therese, Dubbelaar Marissa Lisa, Niederer Rebekka, Luimstra Jolien J, Pop Oltin, Jochum Ann-Kristin, Purde Mette-Triin, Hasan Ali Omar, Bomze David, Bauer Jens, Freudenmann Lena Katharina, Marcu Ana, Wolfschmitt Eva-Maria, Haen Sebastian, Gross Thorben, Flatz Lukas
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.