PMID- 34638461
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211016
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 19
DP  - 2021 Oct 4
TI  - Alterations in HLA Class I-Presented Immunopeptidome and Class I-Interactome upon 
      Osimertinib Resistance in EGFR Mutant Lung Adenocarcinoma.
LID - 10.3390/cancers13194977 [doi]
LID - 4977
AB  - Immune checkpoint inhibitor (ICI) therapy has been a paradigm shift in the 
      treatment of cancer. ICI therapy results in durable responses and survival 
      benefit for a large number of tumor types. Osimertinib, a third-generation 
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has shown 
      great efficacy treating EGFR mutant lung cancers; however, all patients 
      eventually develop resistance. ICI therapy has not benefitted EGFR mutant lung 
      cancer. Herein, we employed stable isotope labeling by amino acids in cell 
      culture (SILAC) quantitative mass spectrometry-based proteomics to investigate 
      potential immune escape molecular mechanisms in osimertinib resistant EGFR mutant 
      lung adenocarcinoma by interrogating the alterations in the human leukocyte 
      antigen (HLA) Class I-presented immunopeptidome, Class I-interactome, and the 
      whole cell proteome between isogenic osimertinib-sensitive and -resistant human 
      lung adenocarcinoma cells. Our study demonstrates an overall reduction in HLA 
      class I-presented immunopeptidome and downregulation of antigen presentation core 
      complex (e.g., TAP1 and ERAP1/2) and immunoproteasome in osimertinib resistant 
      lung adenocarcinoma cells. Several key components in autophagy pathway are 
      differentially altered. S100 proteins and SLC3A2 may play critical roles in 
      reduced antigen presentation. Our dataset also includes ~1000 novel HLA class I 
      interaction partners and hundreds of Class I-presented immunopeptides in EGFR 
      mutant lung adenocarcinoma. This large-scale unbiased proteomics study provides 
      novel insights and potential mechanisms of immune evasion of EGFR mutant lung 
      adenocarcinoma.
FAU - Qi, Yue A
AU  - Qi YA
AUID- ORCID: 0000-0003-1914-8710
AD  - Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, 
      Bethesda, MD 20892, USA.
AD  - Center for Alzheimer's and Related Dementias, National Institute on Aging, NIH, 
      Bethesda, MD 20892, USA.
FAU - Maity, Tapan K
AU  - Maity TK
AD  - Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, 
      Bethesda, MD 20892, USA.
FAU - Gao, Shaojian
AU  - Gao S
AD  - Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, 
      Bethesda, MD 20892, USA.
FAU - Gong, Tao
AU  - Gong T
AD  - Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, 
      Bethesda, MD 20892, USA.
FAU - Bahta, Meriam
AU  - Bahta M
AD  - Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, 
      Bethesda, MD 20892, USA.
FAU - Venugopalan, Abhilash
AU  - Venugopalan A
AD  - Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, 
      Bethesda, MD 20892, USA.
FAU - Zhang, Xu
AU  - Zhang X
AD  - Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, 
      Bethesda, MD 20892, USA.
FAU - Guha, Udayan
AU  - Guha U
AD  - Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, 
      Bethesda, MD 20892, USA.
AD  - Bristol-Myers Squibb, Lawrenceville, NJ 08901, USA.
LA  - eng
GR  - NA/Intramural Research Program of Center of Cancer Research (CCR), National 
      Cancer Institute (NCI) of the U.S. National Institutes of Health/
PT  - Journal Article
DEP - 20211004
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8507780
OTO - NOTNLM
OT  - HLA
OT  - SILAC
OT  - antigen presentation
OT  - immune evasion
OT  - immunopeptidome
OT  - lung adenocarcinoma
OT  - osimertinib resistance
OT  - proteomics
COIS- U.G. has a clinical trial agreement (CTA) with AstraZeneca and had received 
      research funding from AstraZeneca, Aurigene, and Esanex. U.G. is currently an 
      employee of Bristol- Myers Squibb. The other authors have no conflicts of 
      interest to report.
EDAT- 2021/10/14 06:00
MHDA- 2021/10/14 06:01
PMCR- 2021/10/04
CRDT- 2021/10/13 01:02
PHST- 2021/09/13 00:00 [received]
PHST- 2021/10/02 00:00 [accepted]
PHST- 2021/10/13 01:02 [entrez]
PHST- 2021/10/14 06:00 [pubmed]
PHST- 2021/10/14 06:01 [medline]
PHST- 2021/10/04 00:00 [pmc-release]
AID - cancers13194977 [pii]
AID - cancers-13-04977 [pii]
AID - 10.3390/cancers13194977 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Oct 4;13(19):4977. doi: 10.3390/cancers13194977.