RT Journal Article
SR Electronic
T1 Immune surveillance in clinical regression of pre-invasive squamous cell lung cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 833004
DO 10.1101/833004
A1 Adam Pennycuick
A1 Vitor H. Teixeira
A1 Khalid AbdulJabbar
A1 Shan E Ahmed Raza
A1 Tom Lund
A1 Ayse Akarca
A1 Rachel Rosenthal
A1 Christodoulos P. Pipinikas
A1 Henry Lee-Six
A1 Deepak P. Chandrasekharan
A1 Robert E. Hynds
A1 Kate H. C. Gowers
A1 Jake Y. Henry
A1 Celine Denais
A1 Mary Falzon
A1 Sophia Antoniou
A1 Pascal F. Durrenberger
A1 Andrew Furness
A1 Bernadette Carroll
A1 Ricky M. Thakrar
A1 Philip J. George
A1 Teresa Marafioti
A1 Charles Swanton
A1 Christina Thirlwell
A1 Peter J. Campbell
A1 Yinyin Yuan
A1 Sergio A. Quezada
A1 Nicholas McGranahan
A1 Sam M. Janes
YR 2019
UL http://biorxiv.org/content/early/2019/11/10/833004.abstract
AB 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, TGF-beta signalling is overactive, 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. This study identifies mechanisms by which pre-cancerous 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.