@article{c8612e25dcf842b6bd52787a27a56885,
title = "Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features",
abstract = "The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.",
author = "Hitoshi Dejima and Xin Hu and Runzhe Chen and Jiexin Zhang and Junya Fujimoto and Parra, {Edwin R.} and Cara Haymaker and Hubert, {Shawna M.} and Dzifa Duose and Solis, {Luisa M.} and Dan Su and Junya Fukuoka and Kazuhiro Tabata and Pham, {Hoa H.N.} and Nicholas Mcgranahan and Baili Zhang and Jie Ye and Lisha Ying and Latasha Little and Curtis Gumbs and Chow, {Chi Wan} and Estecio, {Marcos Roberto} and Godoy, {Myrna C.B.} and Antonoff, {Mara B.} and Boris Sepesi and Pass, {Harvey I.} and Carmen Behrens and Jianhua Zhang and Vaporciyan, {Ara A.} and Heymach, {John V.} and Paul Scheet and Lee, {J. Jack} and Jia Wu and Futreal, {P. Andrew} and Alexandre Reuben and Humam Kadara and Wistuba, {Ignacio I.} and Jianjun Zhang",
note = "Funding Information: J.J.Z. reports research funding from Merck, Johnson and Johnson, and consultant fees from BMS, Johnson and Johnson, AstraZeneca, Geneplus, OrigMed, Innovent outside the submitted work. I.I.W reports Honoraria from Genentech/Roche, Bayer, Bristol-Myers Squibb, Astra Zeneca/Medimmune, Pfizer, HTG Molecular, Asuragen, Merck, GlaxoSmithKline, Guardant Health, Oncocyte, Flame, and MSD; Research support from Genentech, Oncoplex, HTG Molecular, DepArray, Merck, Bristol-Myers Squibb, Med-immune, Adaptive, Adaptimmune, EMD Serono, Pfizer, Takeda, Amgen, Karus, Johnson & Johnson, Bayer, Iovance, 4D, Novartis, and Akoya. H.K. reports funding to MD Anderson Cancer Center from Johnson and Johnson. J.V.H. reports honorariums from AstraZeneca, Boehringer-Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Guardant Health, Foundation medicine, Hengrui Therapeutics, Eli Lilly, Novartis, Spectrum, EMD Serono, Sanofi, Takeda, Mirati Therapeutics, BMS, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, EMD Serono, Pneuma Respiratory, Kairos Venture Investments, Roche and Leads Biolabs. The other authors declare no competing interests. Funding Information: This study was supported by the MD Anderson Khalifa Scholar Award, the National Cancer Institute of the National Institute of Health Research Project Grant (R01CA234629-01), the AACR-Johnson & Johnson Lung Cancer Innovation Science Grant (18-90-52-ZHAN), the University of Texas MD Anderson Cancer Center Pre-Cancer Atlas Project, the MD Anderson Physician Scientist Program, the MD Anderson Lung Cancer Moon Shot Program, Sabin Family Foundation Award, Duncan Family Institute Cancer Prevention Research Seed Funding Program, the Cancer Prevention and Research Institute of Texas Multi-Investigator Research Award grant (RP160668) and the UT Lung Specialized Programs of Research Excellence Grant (P50CA70907), Cancer Prevention and Research Institute of Texas (CPRIT) grant RP150079, Rydin Family Research Fund. We thank MD Anderson Cancer Center{\textquoteright}s Epigenomics Profiling Core and its Science Park Next-Generation Sequencing Core (CPRIT Core RP120348) for performing RRBS profiling. We thank Rong Yao, Jinzhen Chen, Sally Boyd, Eric Sisson and Stan Bujnowski for providing excellent technical support for high-performance cluster (HPC) resource (http://hpcweb.mdanderson.edu/citing.html). We thank Mrs. Sophie Rydin, a fearless cancer fighter for her generous support to lung cancer prevention research. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-22890-x",
language = "English (US)",
volume = "12",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}