Multi-omics analysis reveals neoantigen-independent immune cell infiltration in copy-number driven cancers

Daniel J. McGrail, Lorenzo Federico, Yongsheng Li, Hui Dai, Yiling Lu, Gordon Mills, Song Yi, Shiaw Yih Lin, Nidhi Sahni

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

To realize the full potential of immunotherapy, it is critical to understand the drivers of tumor infiltration by immune cells. Previous studies have linked immune infiltration with tumor neoantigen levels, but the broad applicability of this concept remains unknown. Here, we find that while this observation is true across cancers characterized by recurrent mutations, it does not hold for cancers driven by recurrent copy number alterations, such as breast and pancreatic tumors. To understand immune invasion in these cancers, we developed an integrative multi-omics framework, identifying the DNA damage response protein ATM as a driver of cytokine production leading to increased immune infiltration. This prediction was validated in numerous orthogonal datasets, as well as experimentally in vitro and in vivo by cytokine release and immune cell migration. These findings demonstrate diverse drivers of immune cell infiltration across cancer lineages and may facilitate the clinical adaption of immunotherapies across diverse malignancies.

Original languageEnglish (US)
Article number1317
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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infiltration
Infiltration
cancer
Tumors
tumors
cells
Neoplasms
Ataxia Telangiectasia Mutated Proteins
Cytokines
asynchronous transfer mode
Immunotherapy
mutations
breast
deoxyribonucleic acid
damage
proteins
DNA
DNA Damage
Cell Movement
predictions

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Multi-omics analysis reveals neoantigen-independent immune cell infiltration in copy-number driven cancers. / McGrail, Daniel J.; Federico, Lorenzo; Li, Yongsheng; Dai, Hui; Lu, Yiling; Mills, Gordon; Yi, Song; Lin, Shiaw Yih; Sahni, Nidhi.

In: Nature Communications, Vol. 9, No. 1, 1317, 01.12.2018.

Research output: Contribution to journalArticle

McGrail, Daniel J. ; Federico, Lorenzo ; Li, Yongsheng ; Dai, Hui ; Lu, Yiling ; Mills, Gordon ; Yi, Song ; Lin, Shiaw Yih ; Sahni, Nidhi. / Multi-omics analysis reveals neoantigen-independent immune cell infiltration in copy-number driven cancers. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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