Keratinocyte differentiation antigen-specific T cells in immune checkpoint inhibitor-treated NSCLC patients are associated with improved survival. (1st January 2021)

• Record Type: Journal Article
• Authors: Berner, Fiamma; Niederer, Rebekka; Luimstra, Jolien J.; Pop, Oltin Tiberiu; 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; Dubbelaar, Marissa Lisa; Abdou, Marie-Therese; Baumgaertner, Petra; 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; Flatz, Lukas;
• Is Part Of: Oncoimmunology. Volume 10:Number 1(2021)
• Publication Date: 2021-01-01
• Subjects: Immune checkpoint inhibitor therapy -- NSCLC -- tumor-associated antigen -- autoimmune toxicity; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2021.2006893
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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 ex vivo 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.