NSCLC（非小细胞肺癌）患者的最新治疗方法是针对免疫检查点 PD-1（程序性细胞死亡 1）和 PD-L1（程序性细胞死亡配体 1）的免疫疗法。 PD-L1是唯一经过验证的免疫治疗疗效预测因素，但它并不完美。一些患者无法从免疫治疗中受益，并且可能会产生原发性或继发性耐药性。本研究旨在根据临床特征和评估免疫治疗疗效的潜在新预测因素，评估接受免疫检查点抑制剂治疗的非小细胞肺癌（NSCLC）患者的肠道抵抗组组成。该研究包括 30 名晚期 NSCLC 患者，19 名晚期 NSCLC 患者。 (57%) 名男性和 11 名 (33%) 名女性接受一线或二线免疫疗法（nivolumab、pembrolizumab 或 atezolizumab）治疗。我们利用高灵敏度的靶向宏基因组学评估了患者的肠道耐药组组成。研究表明，耐药组丰富度与接受免疫治疗的 NSCLC 患者的临床和人口统计学因素相关。吸烟似乎与大环内酯类、林可酰胺类、链阳菌素和万古霉素核心耐药组丰度增加有关。疾病进展患者的耐药组似乎更加丰富和多样化，林可酰胺耐药基因组标记物 (lnuC) 的水平显着更高。耐药基因lnuC、msrD、ermG、aph(6)、fosA与无进展生存期或/和总生存期相关，可能被认为是潜在影响疾病的因素。免疫检查点抑制剂的治疗根据对免疫治疗的反应而有所不同，有几个不同的标志物。由于它可能会影响治疗效果，因此必须进行更深入的检查。版权所有 © 2024 Iwan、Grenda、Bomba、Bielińska、Wasyl、Kieszko、Rolska-Kopińska、Chmielewska、Krawczyk、Rybczyńska-Tkaczyk、Olejnik 和 Milanowski。

The newest method of treatment for patients with NSCLC (non-small cell lung cancer) is immunotherapy directed at the immune checkpoints PD-1 (Programmed Cell Death 1) and PD-L1 (Programmed Cell Death Ligand 1). PD-L1 is the only validated predictor factor for immunotherapy efficacy, but it is imperfect. Some patients do not benefit from immunotherapy and may develop primary or secondary resistance. This study aimed to assess the intestinal resistome composition of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors in the context of clinical features and potentially new prediction factors for assessing immunotherapy efficacy.The study included 30 advanced NSCLC patients, 19 (57%) men and 11 (33%) women treated with first- or second-line immunotherapy (nivolumab, pembrolizumab or atezolizumab). We evaluated the patient's gut resistome composition using the high sensitivity of targeted metagenomics.Studies have shown that resistome richness is associated with clinical and demographic factors of NSCLC patients treated with immunotherapy. Smoking seems to be associated with an increased abundance of macrolides, lincosamides, streptogramins and vancomycin core resistome. The resistome of patients with progression disease appears to be more abundant and diverse, with significantly higher levels of genomic markers of resistance to lincosamides (lnuC). The resistance genes lnuC, msrD, ermG, aph(6), fosA were correlated with progression-free survival or/and overall survival, thus may be considered as factors potentially impacting the disease.The results indicate that the intestinal resistome of NSCLC patients with immune checkpoint inhibitors treatment differs depending on the response to immunotherapy, with several distinguished markers. Since it might impact treatment efficacy, it must be examined more deeply.Copyright © 2024 Iwan, Grenda, Bomba, Bielińska, Wasyl, Kieszko, Rolska-Kopińska, Chmielewska, Krawczyk, Rybczyńska-Tkaczyk, Olejnik and Milanowski.