PMID- 31540894
OWN - NLM
STAT- MEDLINE
DCOM- 20200908
LR  - 20240216
IS  - 2326-6074 (Electronic)
IS  - 2326-6066 (Print)
IS  - 2326-6066 (Linking)
VI  - 7
IP  - 12
DP  - 2019 Dec
TI  - ALK and RET Inhibitors Promote HLA Class I Antigen Presentation and Unmask New 
      Antigens within the Tumor Immunopeptidome.
PG  - 1984-1997
LID - 10.1158/2326-6066.CIR-19-0056 [doi]
AB  - 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.
CI  - (c)2019 American Association for Cancer Research.
FAU - Oh, Claire Y
AU  - Oh CY
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
AD  - Weill Cornell Medicine, New York, New York.
FAU - Klatt, Martin G
AU  - Klatt MG
AUID- ORCID: 0000-0001-8703-7305
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
FAU - Bourne, Christopher
AU  - Bourne C
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
AD  - Weill Cornell Medicine, New York, New York.
FAU - Dao, Tao
AU  - Dao T
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
FAU - Dacek, Megan M
AU  - Dacek MM
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
AD  - Weill Cornell Medicine, New York, New York.
FAU - Brea, Elliott J
AU  - Brea EJ
AUID- ORCID: 0000-0002-6283-0267
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
AD  - Weill Cornell Medicine, New York, New York.
FAU - Mun, Sung Soo
AU  - Mun SS
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
FAU - Chang, Aaron Y
AU  - Chang AY
AUID- ORCID: 0000-0002-7770-7405
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
AD  - Weill Cornell Medicine, New York, New York.
FAU - Korontsvit, Tatyana
AU  - Korontsvit T
AUID- ORCID: 0000-0001-6319-1797
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York.
FAU - Scheinberg, David A
AU  - Scheinberg DA
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      New York. scheinbd@mskcc.org.
AD  - Weill Cornell Medicine, New York, New York.
LA  - eng
GR  - R01 CA055349/CA/NCI NIH HHS/United States
GR  - P01 CA033049/CA/NCI NIH HHS/United States
GR  - P50 CA172012/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - T32 CA062948/CA/NCI NIH HHS/United States
GR  - R35 CA241894/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190920
PL  - United States
TA  - Cancer Immunol Res
JT  - Cancer immunology research
JID - 101614637
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Sulfones)
RN  - 53AH36668S (Crizotinib)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - K418KG2GET (ceritinib)
SB  - IM
MH  - Anaplastic Lymphoma Kinase/*antagonists & inhibitors
MH  - Animals
MH  - Antigen Presentation/drug effects
MH  - Antigens, Neoplasm/*immunology
MH  - Cell Line, Tumor
MH  - Crizotinib/pharmacology
MH  - Female
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Mice, Transgenic
MH  - Neoplasms/immunology
MH  - Peptides/immunology
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins c-ret/*antagonists & inhibitors
MH  - Pyrimidines/pharmacology
MH  - Sulfones/pharmacology
PMC - PMC6891198
MID - NIHMS1540475
EDAT- 2019/09/22 06:00
MHDA- 2020/09/09 06:00
PMCR- 2020/06/01
CRDT- 2019/09/22 06:00
PHST- 2019/01/23 00:00 [received]
PHST- 2019/04/18 00:00 [revised]
PHST- 2019/09/16 00:00 [accepted]
PHST- 2019/09/22 06:00 [pubmed]
PHST- 2020/09/09 06:00 [medline]
PHST- 2019/09/22 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - 2326-6066.CIR-19-0056 [pii]
AID - 10.1158/2326-6066.CIR-19-0056 [doi]
PST - ppublish
SO  - Cancer Immunol Res. 2019 Dec;7(12):1984-1997. doi: 10.1158/2326-6066.CIR-19-0056. 
      Epub 2019 Sep 20.