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

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.

• Authors: Fiamma Berner, Rebekka Niederer, Jolien J Luimstra, Oltin Tiberiu Pop, Ann-Kristin Jochum, Mette-Triin Purde, Omar Hasan Ali, David Bomze, Jens Bauer, Lena Katharina Freudenmann, Ana Marcu, Eva-Maria Wolfschmitt, Sebastian Haen, Thorben Gross, Marissa Lisa Dubbelaar, Marie-Therese Abdou, Petra Baumgaertner, Christina Appenzeller, Caroline Cicin-Sain, Tobias Lenz, Daniel E Speiser, Burkhard Ludewig, Christoph Driessen, Markus Jörger, Martin Früh, Wolfram Jochum, Antonio Cozzio, Hans-Georg Rammensee, Juliane Walz, Jacques Neefjes, Lukas Flatz
• Journal: Oncoimmunology (Oncoimmunology) Vol. 10 Issue 1 Pg. 2006893 ( 2021) ISSN: 2162-402X [Electronic] United States
• PMID: 34858733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

Chemical References

• Antigens, Differentiation
• Immune Checkpoint Inhibitors

Topics

• Antigens, Differentiation (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Humans
• Immune Checkpoint Inhibitors
• Keratinocytes
• Lung Neoplasms (drug therapy)