Immune surveillance in clinical regression of preinvasive squamous cell lung cancer

Adam Pennycuick, Vitor H. Teixeira, Khalid Abduljabbar, Shan E. Ahmed Raza, Tom Lund, Ayse U. Akarca, Rachel Rosenthal, Lukas Kalinke, Deepak P. Chandrasekharan, Christodoulos P. Pipinikas, Henry Lee-Six, Robert E. Hynds, Kate H.C. Gowers, Jake Y. Henry, Fraser R. Millar, Yeman B. Hagos, Celine Denais, Mary Falzon, David A. Moore, Sophia AntoniouPascal F. Durrenberger, Andrew J. Furness, Bernadette Carroll, Claire Marceaux, Marie Liesse Asselin-Labat, William Larson, Courtney Betts, Lisa M. Coussens, Ricky M. Thakrar, Jeremy George, Charles Swanton, Christina Thirlwell, Peter J. Campbell, Teresa Marafioti, Yinyin Yuan, Sergio A. Quezada, Nicholas McGranahan, Sam M. Janes

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Before squamous cell lung cancer develops, precancerous lesions can be found in the airways. From longitudinal monitoring, we know that only half of such lesions become cancer, whereas a third spontaneously regress. Although recent studies have described the presence of an active immune response in high-grade lesions, the mechanisms underpinning clinical regression of precancerous lesions remain unknown. Here, we show that host immune surveillance is strongly implicated in lesion regression. Using bronchoscopic biopsies from human subjects, we find that regressive carcinoma in situ lesions harbor more infiltrating immune cells than those that progress to cancer. Moreover, molecular profiling of these lesions identifies potential immune escape mechanisms specifically in those that progress to cancer: antigen presentation is impaired by genomic and epigenetic changes, CCL27–CCR10 signaling is upregulated, and the immunomodulator TNFSF9 is downregulated. Changes appear intrinsic to the carcinoma in situ lesions, as the adjacent stroma of progressive and regressive lesions are transcriptomically similar. SIGnIFICAnCE: Immune evasion is a hallmark of cancer. For the first time, this study identifies mechanisms by which precancerous lesions evade immune detection during the earliest stages of carcino-genesis and forms a basis for new therapeutic strategies that treat or prevent early-stage lung cancer.

Original languageEnglish (US)
Pages (from-to)1489-1499
Number of pages11
JournalCancer discovery
Volume10
Issue number10
DOIs
StatePublished - Oct 2020

ASJC Scopus subject areas

  • Oncology

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