ALK and RET inhibitors promote HLA class I antigen presentation and unmask new antigens within the tumor immunopeptidome Journal Article

   


Authors: Oh, C. Y.; Klatt, M. G.; Bourne, C.; Dao, T.; Dacek, M. M.; Brea, E. J.; Mun, S. S.; Chang, A. Y.; Korontsvit, T.; Scheinberg, D. A.
Article Title: ALK and RET inhibitors promote HLA class I antigen presentation and unmask new antigens within the tumor immunopeptidome
Abstract: T-cell immunotherapies are often thwarted by the limited presentation of tumor-specific antigens abetted by the downregulation of human leukocyte antigen (HLA). We showed that drugs inhibiting ALK and RET produced dose-related increases in cell-surface HLA in tumor cells bearing these mutated kinases in vitro and in vivo, as well as elevated transcript and protein expression of HLA and other antigen-processing machinery. Subsequent analysis of HLA-presented peptides after ALK and RET inhibitor treatment identified large changes in the immunopeptidome with the appearance of hundreds of new antigens, including T-cell epitopes associated with impaired peptide processing (TEIPP) peptides. ALK inhibition additionally decreased PD-L1 levels by 75%. Therefore, these oncogenes may enhance cancer formation by allowing tumors to evade the immune system by downregulating HLA expression. Altogether, RET and ALK inhibitors could enhance T-cell- based immunotherapies by upregulating HLA, decreasing checkpoint blockade ligands, and revealing new, immunogenic, cancer-associated antigens. © 2019 American Association for Cancer Research.
Journal Title: Cancer Immunology Research
Volume: 7
Issue: 12
ISSN: 2326-6066
Publisher: American Association for Cancer Research  
Date Published: 2019-12-01
Start Page: 1984
End Page: 1997
Language: English
DOI: 10.1158/2326-6066.Cir-19-0056
PUBMED: 31540894
PROVIDER: scopus
PMCID: PMC6891198
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85075963166&doi=10.1158%2f2326-6066.CIR-19-0056&partnerID=40&md5=b1d777f0750546a72c9e185f5b3a739d
Notes: Source: Scopus
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MSK Authors
  1. David Scheinberg
    492 Scheinberg
  2. Tao Dao
    81 Dao
  3. Tatyana Korontsvit
    53 Korontsvit
  4. Elliott Joseph Brea
    17 Brea
  5. Aaron Chang
    15 Chang
  6. Claire Oh
    7 Oh
  7. Megan Dacek
    17 Dacek
  8. Martin Gunther Klatt
    22 Klatt
  9. Sung Soo Mun
    19 Mun
  10. Christopher Bourne
    13 Bourne
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