准确预测哪些诊断为非小细胞肺癌（NSCLC）的患者将对免疫治疗产生反应仍然是一个临床挑战。本研究旨在确定 MYC 免疫反应性、MYC 拷贝数增益 (CNG)、驱动突变和免疫疗法治疗后生存之间的关联，以深入了解临床 MYC 评估是否具有预测价值。在 82 名患有 MYC 的患者中测定了 MYC 拷贝数状态接受免疫疗法治疗的非小细胞肺癌，并对其中 80 例进行了 MYC 免疫组织化学 (IHC) 检测。 ≥40%的肿瘤细胞的MYC染色被认为是阳性。通过回顾性图表审查评估驱动基因改变、PD-L1 状态和生存结果。总生存期（OS）和无进展生存期（PFS）从免疫治疗开始之日起计算。82例病例中有9例（11%）出现MYC CNG，80例免疫染色病例中有56例（70%）MYC呈阳性。 MYC CNG 与 STK11 突变显着相关（P=0.023），而阳性 MYC IHC 与 KRAS 突变（P=0.0076）和当前/既往吸烟（P=0.0007）显着相关。 MYC CNG 和阳性 MYC IHC 彼此之间没有显着相关性（P=0.42），或者与 PD-L1≥1% 没有显着相关性（MYC CNG：P=0.10；MYC IHC：P=0.09）。 MYC IHC 阳性和 PD-L1 ≥1% 都是 OS 的显着预测因子（MYC：HR 2.7，95% CI 1.1-6.4，P=0.026；PD-L1：HR 0.33，95% CI 0.15-0.72，P=0.0055 ）。 MYC IHC 阳性/PD-L1<1% 病例的 OS（中位 230 天与 918 天，P=0.00069）和 PFS（中位 84 天与 254 天，P=0.0087）最短。 MYC CNG 与 OS 或 PFS 无关。我们发现 MYC IHC 阳性是免疫治疗后 OS 缩短的独立预测因子，MYC 阳性/PD-L1 <1% 状态预测免疫治疗反应特别差。我们将 MYC IHC 阳性确定为可能与 NSCLC 治疗选择相关且对未来治疗开发感兴趣的特征。版权所有 © 2024。由 Elsevier B.V. 出版。

Accurately predicting which patients diagnosed with non-small cell lung cancer (NSCLC) will respond to immunotherapy remains a clinical challenge. This study aims to determine the associations between MYC immunoreactivity, MYC copy number gain (CNG), driver mutations and survival following immunotherapy treatment, to provide insight into whether clinical MYC assessment may have predictive value.MYC copy number status was determined in 82 patients with NSCLC treated with immunotherapy, and MYC immunohistochemistry (IHC) was performed on 80 of these cases. MYC staining in ≥ 40 % of tumor cells was considered positive. Driver gene alterations, PD-L1 status and survival outcomes were assessed through retrospective chart review. Overall survival (OS) and progression free survival (PFS) were calculated from the date of immunotherapy initiation.Nine (11 %) of 82 cases had MYC CNG and 56 (70 %) of the 80 immunostained cases were positive for MYC. MYC CNG was significantly associated with STK11 mutation (P=0.023), whereas positive MYC IHC was significantly associated with KRAS mutation (P=0.0076) and current/former smoking (P=0.0007). MYC CNG and positive MYC IHC were not significantly associated with each other (P=0.42), or with PD-L1 ≥ 1 % (MYC CNG: P=0.10; MYC IHC: P=0.09). Positive MYC IHC and PD-L1 ≥ 1 % were both significant predictors of OS (MYC: HR 2.7, 95 % CI 1.1-6.4, P=0.026; PD-L1: HR 0.33, 95 % CI 0.15-0.72, P=0.0055). MYC IHC positive/PD-L1 < 1 % cases had the shortest OS (median 230 versus 918 days, P=0.00069) and PFS (median 84 versus 254 days, P=0.0087). MYC CNG was not associated with OS or PFS.We find that positive MYC IHC is an independent predictor of shorter OS after immunotherapy treatment, with MYC positive/PD-L1 < 1 % status predictive of particularly poor immunotherapy response. We identify positive MYC IHC as a feature of possible relevance to NSCLC treatment selection and of interest for future therapy development.Copyright © 2024. Published by Elsevier B.V.