PMID- 32451349
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20240229
IS  - 1535-9484 (Electronic)
IS  - 1535-9476 (Print)
IS  - 1535-9476 (Linking)
VI  - 19
IP  - 8
DP  - 2020 Aug
TI  - Identification of Tumor Antigens in the HLA Peptidome of Patient-derived 
      Xenograft Tumors in Mouse.
PG  - 1360-1374
LID - S1535-9476(20)34967-7 [pii]
LID - 10.1074/mcp.RA119.001876 [doi]
AB  - Personalized cancer immunotherapy targeting patient-specific cancer/testis 
      antigens (CTA) and neoantigens may benefit from large-scale tumor human leukocyte 
      antigen (HLA) peptidome (immunopeptidome) analysis, which aims to accurately 
      identify antigens presented by tumor cells. Although significant efforts have 
      been invested in analyzing the HLA peptidomes of fresh tumors, it is often 
      impossible to obtain sufficient volumes of tumor tissues for comprehensive HLA 
      peptidome characterization. This work attempted to overcome some of these 
      obstacles by using patient-derived xenograft tumors (PDX) in mice as the tissue 
      sources for HLA peptidome analysis. PDX tumors provide a proxy for the expansion 
      of the patient tumor by re-grafting them through several passages to 
      immune-compromised mice. The HLA peptidomes of human biopsies were compared with 
      those derived from PDX tumors. Larger HLA peptidomes were obtained from the 
      significantly larger PDX tumors as compared with the patient biopsies. The HLA 
      peptidomes of different PDX tumors derived from the same source tumor biopsy were 
      very reproducible, even following subsequent passages to new naive mice. Many 
      CTA-derived HLA peptides were discovered, as well as several potential 
      neoantigens/variant sequences. Taken together, the use of PDX tumors for HLA 
      peptidome analysis serves as a highly expandable and stable source of 
      reproducible and authentic peptidomes, opening up new opportunities for defining 
      large HLA peptidomes when only small tumor biopsies are available. This approach 
      provides a large source for tumor antigens identification, potentially useful for 
      personalized immunotherapy.
CI  - (c) 2020 Rijensky et al.
FAU - Rijensky, Nataly Mancette
AU  - Rijensky NM
AD  - Department of Biology, Technion-Israel Institute of Technology Haifa, Israel.
FAU - Blondheim Shraga, Netta R
AU  - Blondheim Shraga NR
AD  - The Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
FAU - Barnea, Eilon
AU  - Barnea E
AD  - Department of Biology, Technion-Israel Institute of Technology Haifa, Israel.
FAU - Peled, Nir
AU  - Peled N
AD  - Institute of Oncology, Davidoff Center, Rabin Medical Center and Sackler Faculty 
      of Medicine, Tel-Aviv University, Petah Tikva, Israel.
FAU - Rosenbaum, Eli
AU  - Rosenbaum E
AD  - Institute of Oncology, Davidoff Center, Rabin Medical Center and Sackler Faculty 
      of Medicine, Tel-Aviv University, Petah Tikva, Israel.
FAU - Popovtzer, Aron
AU  - Popovtzer A
AD  - Institute of Oncology, Davidoff Center, Rabin Medical Center and Sackler Faculty 
      of Medicine, Tel-Aviv University, Petah Tikva, Israel.
FAU - Stemmer, Solomon M
AU  - Stemmer SM
AD  - Davidoff Center, Rabin Medical Center, Beilinson Campus, Petach Tikva, and 
      Felsentien medical research center, Petach Tikva, and Sackler Faculty of 
      Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Livoff, Alejandro
AU  - Livoff A
AD  - Institute of Pathology, Barzilai University Medical Center, Ashkelon, Israel.
FAU - Shlapobersky, Mark
AU  - Shlapobersky M
AD  - Institute of Pathology, Barzilai University Medical Center, Ashkelon, Israel.
FAU - Moskovits, Neta
AU  - Moskovits N
AD  - Davidoff Center, Rabin Medical Center, Beilinson Campus, Petach Tikva, and 
      Felsentien medical research center, Petach Tikva, Israel.
FAU - Perry, Dafna
AU  - Perry D
AD  - The Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
FAU - Rubin, Eitan
AU  - Rubin E
AD  - Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheva, 
      Israel; The Shraga Segal Department of Microbiology, Immunology and Genetics, 
      Ben-Gurion University of the Negev, Beersheba, Israel.
FAU - Haviv, Itzhak
AU  - Haviv I
AD  - The Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
FAU - Admon, Arie
AU  - Admon A
AD  - Department of Biology, Technion-Israel Institute of Technology Haifa, Israel. 
      Electronic address: admon@technion.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200525
PL  - United States
TA  - Mol Cell Proteomics
JT  - Molecular & cellular proteomics : MCP
JID - 101125647
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA Antigens)
RN  - 0 (Peptides)
RN  - 0 (Proteome)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/*metabolism
MH  - Biopsy
MH  - Cluster Analysis
MH  - Female
MH  - HLA Antigens/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mutation/genetics
MH  - Peptides/*metabolism
MH  - Proteome/*metabolism
MH  - *Xenograft Model Antitumor Assays
PMC - PMC8015002
OTO - NOTNLM
OT  - MHC, major histocompatibility complex
OT  - Mass spectrometry
OT  - PDX, patient-derived xenograft tumors
OT  - cancer biomarker(s)
OT  - cancer/testis antigens
OT  - clinical proteomics
OT  - human leukocyte antigen
OT  - immunology
OT  - peptides
OT  - peptidome
OT  - peptidomics
OT  - personalized medicine
COIS- Conflict of interest-Authors declare no competing interests.
EDAT- 2020/05/27 06:00
MHDA- 2021/05/28 06:00
PMCR- 2020/11/23
CRDT- 2020/05/27 06:00
PHST- 2019/11/18 00:00 [received]
PHST- 2020/05/20 00:00 [revised]
PHST- 2020/05/27 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/05/27 06:00 [entrez]
PHST- 2020/11/23 00:00 [pmc-release]
AID - S1535-9476(20)34967-7 [pii]
AID - 10.1074/mcp.RA119.001876 [doi]
PST - ppublish
SO  - Mol Cell Proteomics. 2020 Aug;19(8):1360-1374. doi: 10.1074/mcp.RA119.001876. 
      Epub 2020 May 25.