PMID- 33968037
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20210927
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - IFNgamma Modulates the Immunopeptidome of Triple Negative Breast Cancer Cells by 
      Enhancing and Diversifying Antigen Processing and Presentation.
PG  - 645770
LID - 10.3389/fimmu.2021.645770 [doi]
LID - 645770
AB  - Peptide vaccination remains a viable approach to induce T-cell mediated killing 
      of tumors. To identify potential T-cell targets for Triple-Negative Breast Cancer 
      (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine 
      interferon-gamma (IFNgamma) on the transcriptome, proteome, and immunopeptidome of the 
      TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified 
      a total of 84,131 peptides from 9,647 source proteins presented by human 
      leukocyte antigen (HLA)-I and HLA-II alleles. Treatment with IFNgamma resulted in a 
      remarkable remolding of the immunopeptidome, with only a 34% overlap between 
      untreated and treated cells across the HLA-I immunopeptidome, and expression of 
      HLA-II only detected on treated cells. IFNgamma increased the overall number, 
      diversity, and abundance of peptides contained within the immunopeptidome, as 
      well increasing the coverage of individual source antigens. The suite of peptides 
      displayed under conditions of IFNgamma treatment included many known tumor associated 
      antigens, with the HLA-II repertoire sampling 17 breast cancer associated 
      antigens absent from those sampled by HLA-I molecules. Quantitative analysis of 
      the transcriptome (10,248 transcripts) and proteome (6,783 proteins) of these 
      cells revealed 229 common proteins and transcripts that were differentially 
      expressed. Most of these represented downstream targets of IFNgamma signaling 
      including components of the antigen processing machinery such as tapasin and HLA 
      molecules. However, these changes in protein expression did not explain the 
      dramatic modulation of the immunopeptidome following IFNgamma treatment. These 
      results demonstrate the high degree of plasticity in the immunopeptidome of TNBC 
      cells following cytokine stimulation and provide evidence that under 
      pro-inflammatory conditions a greater variety of potential HLA-I and HLA-II 
      vaccine targets are unveiled to the immune system. This has important 
      implications for the development of personalized cancer vaccination strategies.
CI  - Copyright (c) 2021 Goncalves, Mullan, Duscharla, Ayala, Croft, Faridi and Purcell.
FAU - Goncalves, Gabriel
AU  - Goncalves G
AD  - Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery 
      Institute, Monash University, Clayton, VIC, Australia.
FAU - Mullan, Kerry A
AU  - Mullan KA
AD  - Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery 
      Institute, Monash University, Clayton, VIC, Australia.
FAU - Duscharla, Divya
AU  - Duscharla D
AD  - Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery 
      Institute, Monash University, Clayton, VIC, Australia.
FAU - Ayala, Rochelle
AU  - Ayala R
AD  - Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery 
      Institute, Monash University, Clayton, VIC, Australia.
FAU - Croft, Nathan P
AU  - Croft NP
AD  - Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery 
      Institute, Monash University, Clayton, VIC, Australia.
FAU - Faridi, Pouya
AU  - Faridi P
AD  - Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery 
      Institute, Monash University, Clayton, VIC, Australia.
FAU - Purcell, Anthony W
AU  - Purcell AW
AD  - Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery 
      Institute, Monash University, Clayton, VIC, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210422
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA Antigens)
RN  - 0 (Peptides)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigen Presentation/*drug effects
MH  - Antigens, Neoplasm/immunology
MH  - Cancer Vaccines/immunology
MH  - Cell Line, Tumor
MH  - Female
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Interferon-gamma/*pharmacology
MH  - Peptides/immunology
MH  - Proteomics
MH  - Transcriptome
MH  - Triple Negative Breast Neoplasms/*immunology
PMC - PMC8100505
OTO - NOTNLM
OT  - cytokine stimulation
OT  - human leukocyte antigen
OT  - immunopeptidomics
OT  - mass spectrometry
OT  - proteomics
OT  - transcriptomics
OT  - triple negative breast cancer
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/05/11 06:00
MHDA- 2021/09/28 06:00
PMCR- 2021/01/01
CRDT- 2021/05/10 06:21
PHST- 2020/12/24 00:00 [received]
PHST- 2021/03/26 00:00 [accepted]
PHST- 2021/05/10 06:21 [entrez]
PHST- 2021/05/11 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.645770 [doi]
PST - epublish
SO  - Front Immunol. 2021 Apr 22;12:645770. doi: 10.3389/fimmu.2021.645770. eCollection 
      2021.