PMID- 35121931
OWN - NLM
STAT- MEDLINE
DCOM- 20220414
LR  - 20220421
IS  - 2662-1347 (Electronic)
IS  - 2662-1347 (Linking)
VI  - 1
IP  - 12
DP  - 2020 Dec
TI  - Mutational landscape influences immunotherapy outcomes among patients with 
      non-small-cell lung cancer with human leukocyte antigen supertype B44.
PG  - 1167-1175
LID - 10.1038/s43018-020-00140-1 [doi]
AB  - Human leukocyte antigen (HLA)-B has been recognized as a major determinant of 
      discrepancies in disease outcomes, and recent evidence indicates a role in immune 
      checkpoint blockade (ICB) efficacy. The B44 supertype, which features an 
      electropositive binding pocket that preferentially displays peptides with 
      negatively charged amino acid anchors, is associated with improved survival in 
      ICB-treated melanoma. Yet this effect was not seen in ICB-treated non-small-cell 
      lung cancer (NSCLC). Here we show that mutations leading to glutamic acid 
      substitutions occur more often in melanoma than NSCLC based on mutational 
      landscape. We additionally show stratifying B44 based on the presence of somatic 
      mutations that lead to negatively charged glutamic acid anchors identifies 
      patients with NSCLC with an ICB benefit similar to that seen in melanoma. We 
      anticipate these findings could improve assessment of HLA-related outcomes and 
      prediction of ICB benefit in those with B44, representing approximately half of 
      the world's population.
CI  - (c) 2020. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Cummings, Amy L
AU  - Cummings AL
AUID- ORCID: 0000-0003-0472-392X
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Gukasyan, Jaklin
AU  - Gukasyan J
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Lu, Henry Y
AU  - Lu HY
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Grogan, Tristan
AU  - Grogan T
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Sunga, Gemalene
AU  - Sunga G
AD  - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine 
      at the University of California, Los Angeles, Los Angeles, CA, USA.
FAU - Fares, Charlene M
AU  - Fares CM
AUID- ORCID: 0000-0002-7003-5917
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Hornstein, Nicholas
AU  - Hornstein N
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Zaretsky, Jesse
AU  - Zaretsky J
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Carroll, James
AU  - Carroll J
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Bachrach, Benjamin
AU  - Bachrach B
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Akingbemi, Wisdom O
AU  - Akingbemi WO
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Li, Debory
AU  - Li D
AUID- ORCID: 0000-0002-9820-2975
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Noor, Zorawar
AU  - Noor Z
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Lisberg, Aaron
AU  - Lisberg A
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Goldman, Jonathan W
AU  - Goldman JW
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Elashoff, David
AU  - Elashoff D
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Bui, Alex A T
AU  - Bui AAT
AD  - Department of Radiology, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Ribas, Antoni
AU  - Ribas A
AUID- ORCID: 0000-0003-3669-8458
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Dubinett, Steven M
AU  - Dubinett SM
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Rossetti, Maura
AU  - Rossetti M
AD  - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine 
      at the University of California, Los Angeles, Los Angeles, CA, USA.
FAU - Garon, Edward B
AU  - Garon EB
AUID- ORCID: 0000-0001-7077-8801
AD  - Department of Medicine, David Geffen School of Medicine at the University of 
      California, Los Angeles, Los Angeles, CA, USA. egaron@mednet.ucla.edu.
LA  - eng
GR  - R01 CA208403/CA/NCI NIH HHS/United States
GR  - K08 CA245249/CA/NCI NIH HHS/United States
GR  - R01 CA28403/Center for Strategic Scientific Initiatives, National Cancer 
      Institute (NCI Center for Strategic Scientific Initiatives)/
GR  - P01 CA244118/CA/NCI NIH HHS/United States
GR  - R35 CA197633/CA/NCI NIH HHS/United States
GR  - R01 CA226079/CA/NCI NIH HHS/United States
GR  - U01 CA196408/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201116
PL  - England
TA  - Nat Cancer
JT  - Nature cancer
JID - 101761119
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B44 Antigen)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
CIN - Nat Cancer. 2020 Dec;1(12):1132-1133. PMID: 35121934
MH  - *Carcinoma, Non-Small-Cell Lung/genetics
MH  - Glutamic Acid/genetics
MH  - HLA-B Antigens/genetics
MH  - HLA-B44 Antigen/genetics
MH  - Humans
MH  - Immunotherapy
MH  - *Lung Neoplasms/genetics
MH  - *Melanoma/genetics
MH  - Mutation
EDAT- 2020/12/01 00:00
MHDA- 2022/04/15 06:00
CRDT- 2022/02/05 05:49
PHST- 2020/04/15 00:00 [received]
PHST- 2020/10/06 00:00 [accepted]
PHST- 2022/02/05 05:49 [entrez]
PHST- 2020/12/01 00:00 [pubmed]
PHST- 2022/04/15 06:00 [medline]
AID - 10.1038/s43018-020-00140-1 [pii]
AID - 10.1038/s43018-020-00140-1 [doi]
PST - ppublish
SO  - Nat Cancer. 2020 Dec;1(12):1167-1175. doi: 10.1038/s43018-020-00140-1. Epub 2020 
      Nov 16.