The Immune Contexture Associates with the Genomic Landscape in Lung Adenomatous Premalignancy
Abstract
Epithelial cells in the field of lung injury can give rise to distinct premalignant lesions that may bear unique genetic aberrations. A subset of these lesions may escape immune surveillance and progress to invasive cancer; however, the mutational landscape that may predict progression has not been determined. Knowledge of premalignant lesion composition and the associated microenvironment is critical for understanding tumorigenesis and the development of effective preventive and interception strategies. To identify somatic mutations and the extent of immune cell infiltration in adenomatous premalignancy and associated lung adenocarcinomas, we sequenced exomes from 41 lung cancer resection specimens, including 89 premalignant atypical adenomatous hyperplasia lesions, 15 adenocarcinomas in situ, and 55 invasive adenocarcinomas and their adjacent normal lung tissues. We defined nonsynonymous somatic mutations occurring in both premalignancy and the associated tumor as progression-associated mutations whose predicted neoantigens were highly correlated with infiltration of CD8+ and CD4+ T cells as well as upregulation of PD-L1 in premalignant lesions, suggesting the presence of an adaptive immune response to these neoantigens. Each patient had a unique repertoire of somatic mutations and associated neoantigens. Collectively, these results provide evidence for mutational heterogeneity, pathway dysregulation, and immune recognition in pulmonary premalignancy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 01, 2019
- Source ID
- 10.1158/0008-5472.can-19-0153
Entities
People
- Arum E. Spira
- Atsuko Seki
- Brandon S. Grimes
- Brian K. Gardner
- David A. Elashoff
- Denise R. Aberle
- Gregory A Fishbein
- Jane Yanagawa
- Jay M. Lee
- Kostyantyn Krysan
- Linh Tran
- Ramin Salehi-rad
- Sherven Sharma
- Steven M. Dubinett
- Tonya C. Walser
- William D. Wallace
Organizations
- Boston University
- National Cancer Institute
- National Institutes of Health
- Tobacco-Related Disease Research Program
- UCLA David Geffen School of Medicine
- United States Department of Defense
- University of California, Los Angeles