TY - JOUR
T1 - Geospatial immune variability illuminates differential evolution of lung adenocarcinoma
AU - TRACERx Consortium
AU - AbdulJabbar, Khalid
AU - Raza, Shan E.Ahmed
AU - Rosenthal, Rachel
AU - Jamal-Hanjani, Mariam
AU - Veeriah, Selvaraju
AU - Akarca, Ayse
AU - Lund, Tom
AU - Moore, David A.
AU - Salgado, Roberto
AU - Al-Bakir, Maise
AU - Zapata, Luis
AU - Hiley, Crispin T.
AU - Officer, Leah
AU - Sereno, Marco
AU - Smith, Claire Rachel
AU - Loi, Sherene
AU - Hackshaw, Allan
AU - Marafioti, Teresa
AU - Quezada, Sergio A.
AU - McGranahan, Nicholas
AU - Le Quesne, John
AU - Swanton, Charles
AU - Jamal-Hanjani, Mariam
AU - Le Quesne, John
AU - Hackshaw, Allan
AU - Quezada, Sergio A.
AU - McGranahan, Nicholas
AU - Rosenthal, Rachel
AU - Hiley, Crispin T.
AU - Veeriah, Selvaraju
AU - Moore, David A.
AU - Salgado, Roberto
AU - Ngai, Yenting
AU - Sharp, Abigail
AU - Rodrigues, Cristina
AU - Pressey, Oliver
AU - Smith, Sean
AU - Gower, Nicole
AU - Dhanda, Harjot
AU - Riley, Joan
AU - Primrose, Lindsay
AU - Martinson, Luke
AU - Carey, Nicolas
AU - Shaw, Jacqui A.
AU - Fennell, Dean
AU - Wilson, Gareth A.
AU - Birkbak, Nicolai J.
AU - Watkins, Thomas B.K.
AU - Van Loo, Peter
AU - Yuan, Yinyin
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1–5. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort6. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer–stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes.
AB - Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1–5. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort6. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer–stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes.
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U2 - 10.1038/s41591-020-0900-x
DO - 10.1038/s41591-020-0900-x
M3 - Article
C2 - 32461698
AN - SCOPUS:85087994512
SN - 1078-8956
VL - 26
SP - 1054
EP - 1062
JO - Nature medicine
JF - Nature medicine
IS - 7
ER -