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.