Immunotherapy with immune checkpoint inhibitors (ICIs) represents a major breakthrough in lung cancer treatment. For patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status (PS), the availability of sensitivity markers to immune-checkpoint inhibitors (ICI) would be useful for attending physicians and assist them in their decision-making process. Deficient mismatch repair (dMMR) can lead to high microsatellite instability (MSI-H) and coexist with mutations in polymerase proofreading (DNA polymerase Epsilon POLE and delta 1 POLD1) with a specific mutational signature. This would result in high tumor mutational burden and programmed cell death protein ligand 1 (PD-L1) overexpression. We report herein on a NSCLC case with MSI-H and POLE mutation in a patient with inaugural poor general condition, who exhibited prolonged response to anti-programmed cell death protein (PD-1) therapy. Additionally, there was a marked improvement of the patient’s performance status, from PS 3 before ICI administration to PS 1 upon ICI therapy.

免疫检查点抑制剂 (ICIs) 的免疫治疗代表了肺癌治疗的重大突破。对于晚期非小细胞肺癌 (NSCLC) 和体能状态 (PS) 较差的患者，免疫检查点抑制剂 (ICI) 敏感性标志物的可用性将有助于主治医生并协助他们做出决策. 错配修复缺陷 (dMMR) 可导致高度微卫星不稳定性 (MSI-H)，并与具有特定突变特征的聚合酶校对突变（DNA 聚合酶 Epsilon POLE 和 delta 1 POLD1）共存。这将导致高肿瘤突变负荷和程序性细胞死亡蛋白配体 1 (PD-L1) 过度表达。我们在此报告了一例具有 MSI-H 和 POLE 突变的 NSCLC 病例，该病例的患者就诊时全身状况不佳，他们对抗程序性细胞死亡蛋白 (PD-1) 治疗表现出延长的反应。此外，患者的体能状态有显着改善，从 ICI 给药前的 PS 3 到 ICI 治疗后的 PS 1。