Immune surveillance in clinical regression of pre-invasive squamous cell lung cancer
| Autor: | Christodoulos P. Pipinikas, Ricky Thakrar, Sergio A. Quezada, Vitor H. Teixeira, Sophia Antoniou, Adam Pennycuick, Jeremy George, Lukas Kalinke, Yinyin Yuan, Robert E. Hynds, Henry Lee-Six, Sam M. Janes, Fraser R. Millar, Celine Denais, Shan E Ahmed Raza, Andrew Furness, Jake Y. Henry, Nicholas McGranahan, Ayse Akarca, Christina Thirlwell, Claire Marceaux, Yeman Brhane Hagos, Lisa M. Coussens, Pascal F. Durrenberger, Marie Liesse Asselin-Labat, Peter J. Campbell, Charles Swanton, Khalid AbdulJabbar, Teresa Marafioti, Rachel Rosenthal, Deepak P. Chandrasekharan, Tom Lund, Kate H.C. Gowers, David A Moore, Mary Falzon, Bernadette Carroll, William Larson, Courtney Betts |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty business.industry Antigen presentation medicine.disease Q1 3. Good health Lesion 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system Oncology Stroma 030220 oncology & carcinogenesis Carcinoma medicine CCR10 CCL27 Epigenetics medicine.symptom business RC |
| ISSN: | 2159-8274 |
| Popis: | 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 carcinogenesis and forms a basis for new therapeutic strategies that treat or prevent early-stage lung cancer. See related commentary by Krysan et al., p. 1442. This article is highlighted in the In This Issue feature, p. 1426 |
| Databáze: | OpenAIRE |
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