PMID- 30780001
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20200721
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 14
IP  - 6
DP  - 2019 Jun
TI  - PD-L1 Expression, Tumor Mutational Burden, and Cancer Gene Mutations Are Stronger 
      Predictors of Benefit from Immune Checkpoint Blockade than HLA Class I Genotype 
      in Non-Small Cell Lung Cancer.
PG  - 1021-1031
LID - S1556-0864(19)30116-9 [pii]
LID - 10.1016/j.jtho.2019.02.008 [doi]
AB  - INTRODUCTION: Immune checkpoint blockade (ICB) has revolutionized the treatment 
      of NSCLC, but only approximately 15% of patients achieve durable benefit. 
      Understanding mechanisms of resistance to ICB is pivotal in developing more 
      effective treatment strategies. Recent studies showed that human leukocyte 
      antigen (HLA) class I heterozygosity might be important in mediating benefit from 
      ICB. We aimed to investigate the impact of HLA class I genotype on outcomes of 
      patients with NSCLC treated with ICB. METHODS: We collected HLA typing, genomic, 
      and clinical data from patients with advanced NSCLC treated with ICB at M. D. 
      Anderson Cancer Center. We compared HLA class I-heterozygous and HLA class 
      I-homozygous patients for progression-free survival (PFS) and overall survival 
      (OS). HLA I supertype/alleles were also analyzed. To validate our findings, we 
      also analyzed two previously published independent cohorts of patients with NSCLC 
      (the CheckMate-012 and Chowell cohorts). RESULTS: No significant correlations 
      were observed for HLA class I zygosity and PFS or OS in the M. D. Anderson Cancer 
      Center (n = 200), CheckMate-012 (n = 75), or Chowell (n = 371) cohorts. No HLA 
      class I supertype/allele was consistently shown to be correlated with PFS or OS. 
      Predictors of worse outcome across the three cohorts included presence of 
      targetable driver mutation, serine/threonine kinase 11 gene (STK11) mutation, 
      negative programmed death ligand 1 expression, and low tumor mutational burden. 
      CONCLUSIONS: HLA class I genotype is not correlated with survival in advanced 
      NSCLC treated with ICB. This suggests that the impact of HLA class I diversity 
      may be disease specific and that tumor genomic and immune markers are more 
      impactful in predicting benefit from ICB in NSCLC.
CI  - Copyright (c) 2019 International Association for the Study of Lung Cancer. 
      Published by Elsevier Inc. All rights reserved.
FAU - Negrao, Marcelo V
AU  - Negrao MV
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Lam, Vincent K
AU  - Lam VK
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Reuben, Alexandre
AU  - Reuben A
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Rubin, Maria Laura
AU  - Rubin ML
AD  - Department of Biostatistics, The University of Texas M. D. Anderson Cancer 
      Center, Houston, Texas.
FAU - Landry, Lara Lacerda
AU  - Landry LL
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Roarty, Emily B
AU  - Roarty EB
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Rinsurongkawong, Waree
AU  - Rinsurongkawong W
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Lewis, Jeff
AU  - Lewis J
AD  - Department of Biostatistics, The University of Texas M. D. Anderson Cancer 
      Center, Houston, Texas.
FAU - Roth, Jack A
AU  - Roth JA
AD  - Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. 
      Anderson Cancer Center, Houston, Texas.
FAU - Swisher, Stephen G
AU  - Swisher SG
AD  - Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. 
      Anderson Cancer Center, Houston, Texas.
FAU - Gibbons, Don L
AU  - Gibbons DL
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Wistuba, Ignacio I
AU  - Wistuba II
AD  - Department of Translational Molecular Pathology, The University of Texas M. D. 
      Anderson Cancer Center, Houston, Texas.
FAU - Papadimitrakopoulou, Vassiliki
AU  - Papadimitrakopoulou V
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Glisson, Bonnie S
AU  - Glisson BS
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Blumenschein, George R Jr
AU  - Blumenschein GR Jr
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Lee, J Jack
AU  - Lee JJ
AD  - Department of Biostatistics, The University of Texas M. D. Anderson Cancer 
      Center, Houston, Texas.
FAU - Heymach, John V
AU  - Heymach JV
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas.
FAU - Zhang, Jianjun
AU  - Zhang J
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas. Electronic address: 
      jzhang20@mdanderson.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190216
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CD274 protein, human)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents, Immunological/*therapeutic use
MH  - B7-H1 Antigen/*biosynthesis/immunology
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/immunology/pathology
MH  - Cohort Studies
MH  - Female
MH  - Genotype
MH  - HLA Antigens/*genetics/immunology
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/*genetics/immunology/pathology
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Predictive Value of Tests
MH  - Progression-Free Survival
MH  - Tumor Burden
OTO - NOTNLM
OT  - HLA class I
OT  - Immunotherapy
OT  - Lung cancer
OT  - PD-L1
OT  - Tumor mutational burden
EDAT- 2019/02/20 06:00
MHDA- 2020/07/22 06:00
CRDT- 2019/02/20 06:00
PHST- 2018/12/19 00:00 [received]
PHST- 2019/02/01 00:00 [revised]
PHST- 2019/02/11 00:00 [accepted]
PHST- 2019/02/20 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2019/02/20 06:00 [entrez]
AID - S1556-0864(19)30116-9 [pii]
AID - 10.1016/j.jtho.2019.02.008 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2019 Jun;14(6):1021-1031. doi: 10.1016/j.jtho.2019.02.008. Epub 
      2019 Feb 16.