Immune surveillance in clinical regression of pre-invasive squamous cell lung cancer
Authors listAdam 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 Rob Hynds Kate HC Gowers Jake Y Henry Fraser R Millar Yeman B Hagos Celine Denais Mary Falzon David A Moore Sophia Antoniou Pascal F Durrenberger Andrew JS 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
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Before squamous cell lung cancer develops, pre-cancerous 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. While recent studies have described the presence of an active immune response in high-grade lesions, the mechanisms underpinning clinical regression of pre-cancerous 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 harbour 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 signalling is upregulated, and the immunomodulator TNFSF9 is downregulated. Changes appear intrinsic to the CIS lesions as the adjacent stroma of progressive and regressive lesions are transcriptomically similar.
Journal Cancer Discovery
Pages Epub ahead of print