Department of Thoracic Oncology, Cancer Center, West China Hospital, Medical School, Sichuan University, Chengdu, China.
Department of pathology, West China Hospital, Medical School, Sichuan University, Chengdu, China.
Ann Palliat Med. 2021 Jun;10(6):7088-7094. doi: 10.21037/apm-20-1639. Epub 2021 Mar 23.
Immune checkpoint inhibitors (ICI) monotherapy or combination therapies have become increasingly popular in patients with advanced non-small cell lung cancer (NSCLC). However, there are still many unknowns concerning the predictive bio-markers and resistance mechanisms to immunotherapy. Patients with primary tumor STK11 mutation reportedly to have a lower response rate than the STK11 wild-type and possibly a primary resistance mechanism to ICIs. However, there is presently no data regarding the contribution of STK11 to acquired resistance to ICIs. Herein we report on a patient who was diagnosed with advanced lung squamous cell carcinoma accompanied by Lynch syndrome. The patient developed an STK11 mutation after receiving pembrolizumab as a first-line treatment. Programmed death ligand 1 (PD-L1) was highly expressed (50%) in the biopsy. HRAS Q61L and TP53 R158L were mainly detected. Unexpectedly, the patient carried an MSH6 heterozygous germline mutation, and was classified as proficient mismatch repair (pMMR). The patient subsequently received pembrolizumab (200 mg, ivgtt, q3w) as first line therapy and achieved stable disease (SD) as the best response. After eight treatment cycles, the patient suffered disease progression (PD), and an STK11 frameshift mutation was newly identified in his plasma circulating tumor deoxyribonucleic acid (ctDNA). This case study suggests that STK11 could contribute to pembrolizumab acquired resistance. Furthermore, the patient was also diagnosed with Lynch syndrome, which rarely occurs in lung cancer.
免疫检查点抑制剂（ICI）单药或联合治疗在晚期非小细胞肺癌（NSCLC）患者中越来越受欢迎。然而，免疫治疗的预测生物标志物和耐药机制仍有许多未知之处。据报道，原发肿瘤 STK11 突变的患者对 ICI 的反应率低于 STK11 野生型，可能存在原发性耐药机制。然而，目前尚无关于 STK11 对 ICI 获得性耐药的贡献的数据。在此，我们报告了一例经诊断患有伴林奇综合征的晚期肺鳞状细胞癌的患者。该患者在接受派姆单抗作为一线治疗后发生了 STK11 突变。活检中程序性死亡配体 1（PD-L1）高表达（50%）。主要检测到 HRAS Q61L 和 TP53 R158L。出乎意料的是，该患者携带 MSH6 杂合胚系突变，归类为 proficient mismatch repair（pMMR）。随后，该患者接受派姆单抗（200mg，静脉滴注，q3w）作为一线治疗，最佳反应为疾病稳定（SD）。经过 8 个治疗周期后，患者发生疾病进展（PD），并在其血浆循环肿瘤脱氧核糖核酸（ctDNA）中发现新的 STK11 移码突变。这项病例研究表明，STK11 可能导致派姆单抗获得性耐药。此外，该患者还被诊断患有林奇综合征，这种情况在肺癌中很少见。
