PMID- 32554614
OWN - NLM
STAT- MEDLINE
DCOM- 20210820
LR  - 20210820
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 8
IP  - 1
DP  - 2020 Jun
TI  - Distinctive germline expression of class I human leukocyte antigen (HLA) alleles 
      and DRB1 heterozygosis predict the outcome of patients with non-small cell lung 
      cancer receiving PD-1/PD-L1 immune checkpoint blockade.
LID - 10.1136/jitc-2020-000733 [doi]
LID - e000733
AB  - BACKGROUND: Nivolumab is a human monoclonal antibody against programmed cell 
      death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T 
      lymphocytes (CTLs) restoring their ability to kill target cells expressing 
      specific tumor antigen-derived epitope peptides bound to homologue human 
      leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive 
      therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, 
      in some cases, immune-related adverse events (irAEs). At the present, no reliable 
      biomarkers have been validated to predict either treatment response or adverse 
      events in treated patients. METHODS: We performed a retrospective 
      multi-institutional analysis including 119 patients with mNSCLC who received PD-1 
      blockade since November 2015 to investigate the predictive role of germinal class 
      I HLA and DRB1 genotype. We investigated the correlation among patients' outcome 
      and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse 
      sequence-specific oligonucleotide (SSO) DNA typing. RESULTS: A poor outcome in 
      patients negative for the expression of two most frequent HLA-A alleles was 
      detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 
      12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive 
      patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) 
      of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 
      locus heterozygosis (het) were correlated to a worse OS if we considered het in 
      the locus A; in reverse, long survival was correlated to het in DRB1. 
      CONCLUSIONS: This study demonstrate that class I and II HLA allele 
      characterization to define tumor immunogenicity has relevant implications in 
      predicting nivolumab efficacy in mNSCLC and provide the rationale for further 
      prospective trials of cancer immunotherapy.
CI  - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Correale, Pierpaolo
AU  - Correale P
AD  - Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy michele.caraglia@unicampania.it correalep@yahoo.com.
FAU - Saladino, Rita Emilena
AU  - Saladino RE
AD  - Tissue Typing Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy.
FAU - Giannarelli, Diana
AU  - Giannarelli D
AD  - Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
FAU - Giannicola, Rocco
AU  - Giannicola R
AD  - Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy.
FAU - Agostino, Rita
AU  - Agostino R
AD  - Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy.
FAU - Staropoli, Nicoletta
AU  - Staropoli N
AD  - Medical and Translational Oncology Unit, Department of Experimental and Clinical 
      Medicine, Magna Graecia University, Catanzaro, Italy.
FAU - Strangio, Alessandra
AU  - Strangio A
AD  - Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy.
FAU - Del Giudice, Teresa
AU  - Del Giudice T
AD  - Medical and Translational Oncology Unit, Department of Experimental and Clinical 
      Medicine, Magna Graecia University, Catanzaro, Italy.
FAU - Nardone, Valerio
AU  - Nardone V
AD  - Radiotherapy Unit, "Ospedale del Mare", ASL Napoli 1, Naples, Italy.
FAU - Altomonte, Maria
AU  - Altomonte M
AD  - Unit of Pharmacy, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio 
      Calabria, Italy.
FAU - Pastina, Pierpaolo
AU  - Pastina P
AD  - Section of Radiation Oncology, Medical School, University of Siena, Siena, Italy.
FAU - Tini, Paolo
AU  - Tini P
AD  - Section of Radiation Oncology, Medical School, University of Siena, Siena, Italy.
FAU - Falzea, Antonia Consuelo
AU  - Falzea AC
AD  - Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy.
FAU - Imbesi, Natale
AU  - Imbesi N
AD  - Tissue Typing Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy.
FAU - Arcati, Valentina
AU  - Arcati V
AD  - Tissue Typing Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy.
FAU - Romeo, Giuseppa
AU  - Romeo G
AD  - Tissue Typing Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 
      Reggio Calabria, Italy.
FAU - Caracciolo, Daniele
AU  - Caracciolo D
AD  - Medical and Translational Oncology Unit, Department of Experimental and Clinical 
      Medicine, Magna Graecia University, Catanzaro, Italy.
FAU - Luce, Amalia
AU  - Luce A
AD  - Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, 
      Italy.
FAU - Caraglia, Michele
AU  - Caraglia M
AUID- ORCID: 0000-0003-2408-6091
AD  - Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, 
      Italy michele.caraglia@unicampania.it correalep@yahoo.com.
AD  - Biogem Scarl, Institute of Genetic Research, Laboratory of Precision and 
      Molecular Oncology, Ariano Irpino, Avellino, Italy.
FAU - Giordano, Antonio
AU  - Giordano A
AD  - Sbarro Institute for Cancer Research and Molecular Medicine and Center of 
      Biotechnology, College of Science and Technology, Temple University, 
      Philadelphia, Pennsylvania, USA.
AD  - Department of Medical Biotechnology, University of Siena, Siena, Italy.
FAU - Pirtoli, Luigi
AU  - Pirtoli L
AD  - Sbarro Institute for Cancer Research and Molecular Medicine and Center of 
      Biotechnology, College of Science and Technology, Temple University, 
      Philadelphia, Pennsylvania, USA.
FAU - Necas, Alois
AU  - Necas A
AD  - Central European Institute of Technology, University of Veterinary and 
      Pharmaceutical Sciences, Brno, Czech Republic.
FAU - Amler, Evzen
AU  - Amler E
AD  - Department of Biophysics, 2nd Faculty of Medicine, Charles University in Prague, 
      Prague, Czech Republic.
FAU - Barbieri, Vito
AU  - Barbieri V
AD  - Medical and Translational Oncology Unit, Department of Experimental and Clinical 
      Medicine, Magna Graecia University, Catanzaro, Italy.
FAU - Tassone, Pierfrancesco
AU  - Tassone P
AD  - Medical and Translational Oncology Unit, Department of Experimental and Clinical 
      Medicine, Magna Graecia University, Catanzaro, Italy.
AD  - Sbarro Institute for Cancer Research and Molecular Medicine and Center of 
      Biotechnology, College of Science and Technology, Temple University, 
      Philadelphia, Pennsylvania, USA.
FAU - Tagliaferri, Pierosandro
AU  - Tagliaferri P
AD  - Medical and Translational Oncology Unit, Department of Experimental and Clinical 
      Medicine, Magna Graecia University, Catanzaro, Italy.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (HLA Antigens)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Aged
MH  - Alleles
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/mortality
MH  - Female
MH  - Germ-Line Mutation/*genetics
MH  - HLA Antigens/*metabolism
MH  - Humans
MH  - Immune Checkpoint Inhibitors/pharmacology/*therapeutic use
MH  - Lung Neoplasms/*genetics/mortality
MH  - Male
MH  - Retrospective Studies
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC7304840
OTO - NOTNLM
OT  - B7-H1 antigen
OT  - antigen presentation
OT  - lung neoplasms
OT  - tumor biomarkers
COIS- Competing interests: None declared.
EDAT- 2020/06/20 06:00
MHDA- 2021/08/21 06:00
PMCR- 2020/06/17
CRDT- 2020/06/20 06:00
PHST- 2020/05/05 00:00 [accepted]
PHST- 2020/06/20 06:00 [entrez]
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2021/08/21 06:00 [medline]
PHST- 2020/06/17 00:00 [pmc-release]
AID - jitc-2020-000733 [pii]
AID - 10.1136/jitc-2020-000733 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2020 Jun;8(1):e000733. doi: 10.1136/jitc-2020-000733.