PMID- 35121862
OWN - NLM
STAT- MEDLINE
DCOM- 20220419
LR  - 20230204
IS  - 2662-1347 (Electronic)
IS  - 2662-1347 (Linking)
VI  - 2
IP  - 9
DP  - 2021 Sep
TI  - Negative trade-off between neoantigen repertoire breadth and the specificity of 
      HLA-I molecules shapes antitumor immunity.
PG  - 950-961
LID - 10.1038/s43018-021-00226-4 [doi]
AB  - Human leukocyte antigen class I (HLA-I) genes shape our immune response against 
      pathogens and cancer. Certain HLA-I variants can bind a wider range of peptides 
      than others, a feature that could be favorable against a range of viral diseases. 
      However, the implications of this phenomenon on cancer immune response are 
      unknown. Here we quantified peptide repertoire breadth (or promiscuity) of a 
      representative set of HLA-I alleles and found that patients with cancer who were 
      carrying HLA-I alleles with high peptide-binding promiscuity have significantly 
      worse prognosis after immune checkpoint inhibition. This can be explained by a 
      reduced capacity of the immune system to discriminate tumor neopeptides from 
      self-peptides when patients carry highly promiscuous HLA-I variants, shifting the 
      regulation of tumor-infiltrating T cells from activation to tolerance. In 
      summary, HLA-I peptide-binding specificity shapes neopeptide immunogenicity and 
      the self-immunopeptidome repertoire in an antagonistic manner, and could underlie 
      a negative trade-off between antitumor immunity and genetic susceptibility to 
      viral infections.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Manczinger, Mate
AU  - Manczinger M
AUID- ORCID: 0000-0003-0831-9617
AD  - Biological Research Centre, Institute of Biochemistry, Synthetic and Systems 
      Biology Unit, Eotvos Lorand Research Network (ELKH), Szeged, Hungary. 
      manczinger.mate@brc.hu.
AD  - Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. 
      manczinger.mate@brc.hu.
AD  - MTA-SZTE Dermatological Research Group, Eotvos Lorand Research Network (ELKH), 
      University of Szeged, Szeged, Hungary. manczinger.mate@brc.hu.
AD  - HCEMM-USZ Skin Research Group, Szeged, Hungary. manczinger.mate@brc.hu.
FAU - Koncz, Balazs
AU  - Koncz B
AD  - Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
FAU - Balogh, Gergo Mihaly
AU  - Balogh GM
AD  - Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
FAU - Papp, Benjamin Tamas
AU  - Papp BT
AD  - Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
AD  - Szeged Scientist Academy, Szeged, Hungary.
FAU - Asztalos, Leo
AU  - Asztalos L
AD  - Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
AD  - Szeged Scientist Academy, Szeged, Hungary.
FAU - Kemeny, Lajos
AU  - Kemeny L
AUID- ORCID: 0000-0002-2119-9501
AD  - Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
AD  - MTA-SZTE Dermatological Research Group, Eotvos Lorand Research Network (ELKH), 
      University of Szeged, Szeged, Hungary.
AD  - HCEMM-USZ Skin Research Group, Szeged, Hungary.
FAU - Papp, Balazs
AU  - Papp B
AD  - Biological Research Centre, Institute of Biochemistry, Synthetic and Systems 
      Biology Unit, Eotvos Lorand Research Network (ELKH), Szeged, Hungary.
AD  - HCEMM-BRC Metabolic Systems Biology Lab, Szeged, Hungary.
FAU - Pal, Csaba
AU  - Pal C
AD  - Biological Research Centre, Institute of Biochemistry, Synthetic and Systems 
      Biology Unit, Eotvos Lorand Research Network (ELKH), Szeged, Hungary. 
      cpal@brc.hu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210708
PL  - England
TA  - Nat Cancer
JT  - Nature cancer
JID - 101761119
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
SB  - IM
MH  - Alleles
MH  - *Histocompatibility Antigens Class I/genetics
MH  - Humans
MH  - *Neoplasms/genetics
MH  - Peptides/genetics
MH  - T-Lymphocytes
EDAT- 2022/02/06 06:00
MHDA- 2022/04/20 06:00
CRDT- 2022/02/05 05:49
PHST- 2020/08/11 00:00 [received]
PHST- 2021/05/19 00:00 [accepted]
PHST- 2022/02/05 05:49 [entrez]
PHST- 2022/02/06 06:00 [pubmed]
PHST- 2022/04/20 06:00 [medline]
AID - 10.1038/s43018-021-00226-4 [pii]
AID - 10.1038/s43018-021-00226-4 [doi]
PST - ppublish
SO  - Nat Cancer. 2021 Sep;2(9):950-961. doi: 10.1038/s43018-021-00226-4. Epub 2021 Jul 
      8.