Differential immune profiles distinguish the mutational subtypes of gastrointestinal stromal tumor Journal Article

Authors: Vitiello, G. A.; Bowler, T. G.; Liu, M.; Medina, B. D.; Zhang, J. Q.; Param, N. J.; Loo, J. K.; Goldfeder, R. L.; Chibon, F.; Rossi, F.; Zeng, S.; DeMatteo, R. P.
Article Title: Differential immune profiles distinguish the mutational subtypes of gastrointestinal stromal tumor
Abstract: Gastrointestinal stromal tumor (GIST) is the most common human sarcoma, frequently characterized by an oncogenic mutation in the KIT or PDGFRA gene. We performed RNA sequencing of 75 human GIST tumors from 75 patients, comprising what we believe to be the largest cohort of GISTs sequenced to date, in order to discover differences in the immune infiltrates of KIT- and PDGFRA-mutant GIST. Through bioinformatics, immunohistochemistry, and flow cytometry, we found that in PDGFRA-mutant GISTs, immune cells were more numerous and had higher cytolytic activity than in KIT-mutant GISTs. PDGFRA-mutant GISTs expressed many chemokines, such as CXCL14, at a significantly higher level when compared with KIT-mutant GISTs and exhibited more diverse driver-derived neoepitope:HLA binding, both of which may contribute to PDGFRA-mutant GIST immunogenicity. Through machine learning, we generated gene expression–based immune profiles capable of differentiating KIT- and PDGFRA-mutant GISTs, and identified additional immune features of high–PD-1–and –PD-L1–expressing tumors across all GIST mutational subtypes, which may provide insight into immunotherapeutic opportunities and limitations in GIST. Copyright: © 2019, American Society for Clinical Investigation.
Journal Title: Journal of Clinical Investigation
Volume: 129
Issue: 5
ISSN: 0021-9738
Publisher: American Society for Clinical Investigation  
Date Published: 2019-05-01
Start Page: 1863
End Page: 1877
Language: English
DOI: 10.1172/jci124108
PROVIDER: scopus
PMCID: PMC6486334
PUBMED: 30762585
Notes: Article -- Export Date: 3 June 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Ronald P DeMatteo
    635 DeMatteo
  2. Ferdinando Rossi
    23 Rossi
  3. Shan Zeng
    26 Zeng
  4. Jennifer Qi Zhang
    20 Zhang
  5. Benjamin Medina
    11 Medina
  6. Jennifer Loo
    13 Loo
  7. Timothy Geoffrey Bowler
    7 Bowler
  8. Nesteene Joy Param
    6 Param
  9. Mengyuan Liu
    4 Liu