Integrated Genomic Characterization of the Human Immunome in Cancer.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 11 2020
01 11 2020
Historique:
received:
03
02
2020
revised:
10
07
2020
accepted:
24
08
2020
pubmed:
29
8
2020
medline:
3
2
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Alterations in immune-related pathways are common hallmarks of cancer. A comprehensive understanding of how cancer mutations rewire immune signaling networks and functional output across cancer types is instrumental to realize the full potential of immunotherapy. Here, we systematically interrogated somatic mutations involved in immune signaling that alter immune responses in patients with cancer. To do so, we developed a Network-based Integrative model to Prioritize Potential immune respondER genes (NIPPER). Identified mutations were enriched in essential protein domains and genes identified by NIPPER were associated with responsiveness to multiple immunotherapy modalities. These genes were used to devise an interactome network propagation framework integrated with drug-associated gene signatures to identify potential immunomodulatory drug candidates. Together, our systems-level analysis results help interpret the heterogeneous immune responses among patients and serve as a resource for future functional studies and targeted therapeutics. SIGNIFICANCE: This study demonstrates that integration of multi-omics data can help identify critical molecular determinants for effective targeted therapeutics.
Identifiants
pubmed: 32855206
pii: 0008-5472.CAN-20-0384
doi: 10.1158/0008-5472.CAN-20-0384
pmc: PMC7642109
mid: NIHMS1625329
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4854-4867Subventions
Organisme : NCI NIH HHS
ID : K99 CA240689
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217842
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA191245
Pays : United States
Organisme : NCI NIH HHS
ID : K22 CA214765
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211482
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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