PMID- 29217585
OWN - NLM
STAT- MEDLINE
DCOM- 20180418
LR  - 20240328
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 359
IP  - 6375
DP  - 2018 Feb 2
TI  - Patient HLA class I genotype influences cancer response to checkpoint blockade 
      immunotherapy.
PG  - 582-587
LID - 10.1126/science.aao4572 [doi]
AB  - CD8(+) T cell-dependent killing of cancer cells requires efficient presentation 
      of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, 
      the extent to which patient-specific HLA-I genotype influences response to 
      anti-programmed cell death protein 1 or anti-cytotoxic T lymphocyte-associated 
      protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced 
      cancer patients treated with immune checkpoint blockade (ICB). Maximal 
      heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after 
      ICB compared with patients who were homozygous for at least one HLA locus. In two 
      independent melanoma cohorts, patients with the HLA-B44 supertype had extended 
      survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss 
      of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics 
      simulations of HLA-B*15:01 revealed different elements that may impair CD8(+) T 
      cell recognition of neoantigens. Our results have important implications for 
      predicting response to ICB and for the design of neoantigen-based therapeutic 
      vaccines.
CI  - Copyright (c) 2018 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Chowell, Diego
AU  - Chowell D
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA.
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065, USA.
FAU - Morris, Luc G T
AU  - Morris LGT
AUID- ORCID: 0000-0002-4417-2280
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065, USA.
AD  - Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
FAU - Grigg, Claud M
AU  - Grigg CM
AUID- ORCID: 0000-0001-8847-5366
AD  - NewYork-Presbyterian/Columbia University Medical Center, 177 Fort Washington 
      Avenue, New York, NY 10032, USA.
FAU - Weber, Jeffrey K
AU  - Weber JK
AD  - IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
FAU - Samstein, Robert M
AU  - Samstein RM
AUID- ORCID: 0000-0001-6860-2401
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA.
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065, USA.
FAU - Makarov, Vladimir
AU  - Makarov V
AUID- ORCID: 0000-0001-8026-824X
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA.
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065, USA.
FAU - Kuo, Fengshen
AU  - Kuo F
AUID- ORCID: 0000-0003-1797-2896
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA.
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065, USA.
FAU - Kendall, Sviatoslav M
AU  - Kendall SM
AUID- ORCID: 0000-0002-5368-5109
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA.
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065, USA.
FAU - Requena, David
AU  - Requena D
AUID- ORCID: 0000-0002-5968-1133
AD  - Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 
      10065, USA.
FAU - Riaz, Nadeem
AU  - Riaz N
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA.
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065, USA.
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New 
      York, NY 10065, USA.
FAU - Greenbaum, Benjamin
AU  - Greenbaum B
AD  - Tisch Cancer Institute, Departments of Medicine, Oncological Sciences, and 
      Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
FAU - Carroll, James
AU  - Carroll J
AUID- ORCID: 0000-0002-3061-0761
AD  - David Geffen School of Medicine, University of California, Los Angeles, 2825 
      Santa Monica Boulevard, Suite 200, Santa Monica, CA 90404, USA.
FAU - Garon, Edward
AU  - Garon E
AD  - David Geffen School of Medicine, University of California, Los Angeles, 2825 
      Santa Monica Boulevard, Suite 200, Santa Monica, CA 90404, USA.
FAU - Hyman, David M
AU  - Hyman DM
AUID- ORCID: 0000-0001-8150-9762
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Weill Cornell School of Medicine, New York, NY 10065, USA.
FAU - Zehir, Ahmet
AU  - Zehir A
AUID- ORCID: 0000-0001-5406-4104
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
FAU - Solit, David
AU  - Solit D
AUID- ORCID: 0000-0002-6614-802X
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA.
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan 
      Kettering Cancer Center, New York, NY 10065, USA.
FAU - Berger, Michael
AU  - Berger M
AUID- ORCID: 0000-0003-3882-5000
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA.
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan 
      Kettering Cancer Center, New York, NY 10065, USA.
FAU - Zhou, Ruhong
AU  - Zhou R
AUID- ORCID: 0000-0001-8624-5591
AD  - IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
AD  - Department of Chemistry, Columbia University, New York, NY 10027, USA.
FAU - Rizvi, Naiyer A
AU  - Rizvi NA
AUID- ORCID: 0000-0002-1134-7494
AD  - NewYork-Presbyterian/Columbia University Medical Center, 177 Fort Washington 
      Avenue, New York, NY 10032, USA. chant@mskcc.org nar2144@cumc.columbia.edu.
FAU - Chan, Timothy A
AU  - Chan TA
AUID- ORCID: 0000-0002-9265-0283
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065, USA. chant@mskcc.org nar2144@cumc.columbia.edu.
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065, USA.
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New 
      York, NY 10065, USA.
AD  - Weill Cornell School of Medicine, New York, NY 10065, USA.
LA  - eng
GR  - R01 CA205426/CA/NCI NIH HHS/United States
GR  - K08 DE024774/DE/NIDCR NIH HHS/United States
GR  - R01 CA208403/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P30 CA016042/CA/NCI NIH HHS/United States
GR  - R35 CA232097/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171207
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
CIN - Cancer Discov. 2018 Feb;8(2):139. PMID: 29247014
CIN - Nat Rev Immunol. 2018 Feb;18(2):78-79. PMID: 29279611
CIN - Nat Rev Clin Oncol. 2018 Feb;15(2):66. PMID: 29297507
CIN - Science. 2018 Feb 2;359(6375):516-517. PMID: 29420276
MH  - Adult
MH  - Aged
MH  - Antigen Presentation
MH  - Antigens, Neoplasm/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - CTLA-4 Antigen/*antagonists & inhibitors
MH  - Cancer Vaccines/immunology/therapeutic use
MH  - Cohort Studies
MH  - Genetic Carrier Screening
MH  - Histocompatibility Antigens Class I/chemistry/*genetics
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Melanoma/genetics/*immunology/mortality/*therapy
MH  - Middle Aged
MH  - Programmed Cell Death 1 Receptor/*antagonists & inhibitors
MH  - Protein Conformation
MH  - Skin Neoplasms/genetics/*immunology/mortality/*therapy
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC6057471
MID - NIHMS980063
EDAT- 2017/12/09 06:00
MHDA- 2018/04/19 06:00
PMCR- 2018/07/24
CRDT- 2017/12/09 06:00
PHST- 2017/07/24 00:00 [received]
PHST- 2017/11/29 00:00 [accepted]
PHST- 2017/12/09 06:00 [pubmed]
PHST- 2018/04/19 06:00 [medline]
PHST- 2017/12/09 06:00 [entrez]
PHST- 2018/07/24 00:00 [pmc-release]
AID - science.aao4572 [pii]
AID - 10.1126/science.aao4572 [doi]
PST - ppublish
SO  - Science. 2018 Feb 2;359(6375):582-587. doi: 10.1126/science.aao4572. Epub 2017 
      Dec 7.