Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer.
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ICR Authors
Authors
Pennycuick, A
Teixeira, VH
AbdulJabbar, K
Raza, SEA
Lund, T
Akarca, AU
Rosenthal, R
Kalinke, L
Chandrasekharan, DP
Pipinikas, CP
Lee-Six, H
Hynds, RE
Gowers, KHC
Henry, JY
Millar, FR
Hagos, YB
Denais, C
Falzon, M
Moore, DA
Antoniou, S
Durrenberger, PF
Furness, AJ
Carroll, B
Marceaux, C
Asselin-Labat, M-L
Larson, W
Betts, C
Coussens, LM
Thakrar, RM
George, J
Swanton, C
Thirlwell, C
Campbell, PJ
Marafioti, T
Yuan, Y
Quezada, SA
McGranahan, N
Janes, SM
Teixeira, VH
AbdulJabbar, K
Raza, SEA
Lund, T
Akarca, AU
Rosenthal, R
Kalinke, L
Chandrasekharan, DP
Pipinikas, CP
Lee-Six, H
Hynds, RE
Gowers, KHC
Henry, JY
Millar, FR
Hagos, YB
Denais, C
Falzon, M
Moore, DA
Antoniou, S
Durrenberger, PF
Furness, AJ
Carroll, B
Marceaux, C
Asselin-Labat, M-L
Larson, W
Betts, C
Coussens, LM
Thakrar, RM
George, J
Swanton, C
Thirlwell, C
Campbell, PJ
Marafioti, T
Yuan, Y
Quezada, SA
McGranahan, N
Janes, SM
Document Type
Journal Article
Date
2020-01-01
Date Accepted
2020-07-14
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 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.
Citation
Cancer discovery, 2020, 10 (10), pp. 1489 - 1499
Rights
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
2159-8274
eISSN
2159-8290
Collections
Research Team
Computational Pathology & Integrated Genomics