PMID- 34805368
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220828
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 19
DP  - 2021 Oct
TI  - Homozygous deletion of the HLA-B gene as an acquired-resistance mechanism to 
      nivolumab in a patient with lung adenocarcinoma: a case report.
PG  - 1506
LID - 10.21037/atm-21-3825 [doi]
LID - 1506
AB  - Immune checkpoint inhibitors (ICIs) have greatly improved the treatment of 
      advanced non-small-cell lung cancer, including lung adenocarcinoma (LUAD). 
      Patients treated with ICIs can have long-term clinical outcomes; however, 
      acquired resistance to ICI therapy has been frequently observed. To date, little 
      is known about the underlying mechanisms. In this study, we report the case of a 
      male smoker with metastatic LUAD who initially received multi-line radiotherapy 
      and chemotherapy and achieved stable disease (SD) for almost 10 years. The 
      patient was treated with nivolumab for about 15 months. However, the disease 
      later progressed rapidly. A genetic profile of the patient revealed the 
      homozygous deletion of the human leukocyte antigen (HLA)-B gene, which may have 
      conferred the acquired resistance. Our study is the first to describe the 
      homozygous deletion of the HLA-B gene as an acquired-resistance mechanism to 
      programmed cell death protein 1 (PD-1) blockade in a patient with LUAD. This 
      evidence suggests that tumor cells can selectively lose HLA-A, B, and C to 
      survive under strong immune pressure. This discovery enriches and develops our 
      understanding of the mechanism of drug resistance in ICI therapy in LUAD. 
      However, further investigations are urgently needed to be conducted to determine 
      how this resistance can be overcome.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Zhang, He
AU  - Zhang H
AD  - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Dong, Weiwei
AU  - Dong W
AD  - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Zhao, Huixia
AU  - Zhao H
AD  - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Zeng, Zhiyan
AU  - Zeng Z
AD  - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Zhang, Fengyun
AU  - Zhang F
AD  - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Hu, Yanyan
AU  - Hu Y
AD  - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Li, Qiuwen
AU  - Li Q
AD  - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, 
      Beijing, China.
FAU - Chen, Jing
AU  - Chen J
AD  - ChosenMed Technology (Beijing) Co. Ltd, Beijing, China.
FAU - Meng, Erhong
AU  - Meng E
AD  - ChosenMed Technology (Beijing) Co. Ltd, Beijing, China.
FAU - Xiao, Wenhua
AU  - Xiao W
AD  - Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, 
      Beijing, China.
LA  - eng
PT  - Case Reports
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8573430
OTO - NOTNLM
OT  - Lung adenocarcinoma (LUAD)
OT  - acquired resistance
OT  - case report
OT  - homozygous deletion of HLA-B
OT  - immune checkpoint inhibitors (ICIs)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/atm-21-3825). JC and EM are 
      employees of ChosenMed Technology. The other authors have no conflicts of 
      interest to declare.
EDAT- 2021/11/23 06:00
MHDA- 2021/11/23 06:01
PMCR- 2021/10/01
CRDT- 2021/11/22 06:54
PHST- 2021/07/02 00:00 [received]
PHST- 2021/08/30 00:00 [accepted]
PHST- 2021/11/22 06:54 [entrez]
PHST- 2021/11/23 06:00 [pubmed]
PHST- 2021/11/23 06:01 [medline]
PHST- 2021/10/01 00:00 [pmc-release]
AID - atm-09-19-1506 [pii]
AID - 10.21037/atm-21-3825 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Oct;9(19):1506. doi: 10.21037/atm-21-3825.