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:
Notes: Source: Scopus
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MSK Authors
  1. Tao Dao
    64 Dao
  2. Elliott Joseph Brea
    16 Brea
  3. Aaron   Chang
    13 Chang
  4. Claire   Oh
    7 Oh
  5. Megan Dacek
    3 Dacek
  6. Martin Gunther Klatt
    8 Klatt
  7. Sung Soo Mun
    5 Mun
  8. Christopher Bourne
    1 Bourne