Class II HLA-DRB4 is a predictive biomarker for survival following immunotherapy in metastatic non-small cell lung cancer.
Class II HLA-DRB4 is a predictive biomarker for survival following immunotherapy in metastatic non-small cell lung cancer.
复制标题
DOI：
10.1038/s41598-023-48546-y
复制
发表时间：
2024-01-03
影响因子：
4.6
通讯作者：
Ramnath, Nithya
中科院分区：
文献类型：
--
作者：
Jiang, Cindy Y.;Zhao, Lili;Green, Michael D.;Ravishankar, Shashidhar;Towlerton, Andrea M. H.;Scott, Anthony J.;Raghavan, Malini;Cusick, Matthew F.;Warren, Edus H.;Ramnath, Nithya
免疫检查点抑制剂（ICI）是转移性非小细胞肺癌（mNSCLC）的重要治疗选择。然而，并非所有患者都能从ICI中获益，并可能发生免疫相关不良事件（irAE）。对ICI疗效和毒性的生殖系决定因素的了解有限，但人类白细胞抗原（HLA）基因已成为潜在的预测生物标志物。我们对85例接受ICI治疗的mNSCLC患者进行了HLA分型，并分析了HLA II类基因型对无进展生存期（PFS）、总生存期（OS）和irAE的影响。大多数患者接受帕博利珠单抗治疗（83.5%）。在34/85例（40%）患者中观察到HLA-DRB 4基因型，在单变量（p = 0.022; 26.3个月vs 10.2个月）和多变量分析（p = 0.011，HR 0.49，95% CI [0.29，0.85]）中，其存在与OS改善相关。PFS未达到显著性（单变量，p = 0.12，8.2个月vs 5.1个月）。11例患者发生内分泌irAE。HLA-DRB 4基因型占81.8%（9/11）。HLA-DRB 4患者的内分泌irAE累积发生率较高（p = 0.0139）。我们的研究首次表明，接受ICI治疗的HLA-DRB 4基因型转移性NSCLC患者的生存结局得到改善。HLA-DRB 4患者的中位OS最长（26.3个月）。此外，我们发现HLA-DRB 4与内分泌irAE的发生之间存在相关性。
Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated with improved OS in both univariate (p = 0.022; 26.3 months vs 10.2 months) and multivariate analysis (p = 0.011, HR 0.49, 95% CI [0.29, 0.85]). PFS did not reach significance (univariate, p = 0.12, 8.2 months vs 5.1 months). Eleven patients developed endocrine irAEs. HLA-DRB4 was the predominant genotype among these patients (9/11, 81.8%). Cumulative incidence of endocrine irAEs was higher in patients with HLA-DRB4 (p = 0.0139). Our study is the first to suggest that patients with metastatic NSCLC patients on ICI therapy with HLA-DRB4 genotype experience improved survival outcomes. Patients with HLA-DRB4 had the longest median OS (26.3 months). Additionally, we found a correlation between HLA-DRB4 and the occurrence of endocrine irAEs.
登录
查看更多内容
影响因子：
64.5
作者：
McGranahan N;Rosenthal R;Hiley CT;Rowan AJ;Watkins TBK;Wilson GA;Birkbak NJ;Veeriah S;Van Loo P;Herrero J;Swanton C;TRACERx Consortium
通讯作者：
TRACERx Consortium
DOI：
10.1186/s13046-020-01749-x
发表时间：
2020-12-14
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Jia XH;Geng LY;Jiang PP;Xu H;Nan KJ;Yao Y;Jiang LL;Sun H;Qin TJ;Guo H
通讯作者：
Guo H
影响因子：
8.4
作者：
Ali, Omar Hasan;Berner, Fiamma;Flatz, Lukas
通讯作者：
Flatz, Lukas
影响因子：
2.5
作者：
Dibya Ranjan, Behera;Nand Kumar, Singh;Pramod Kumar, Verma
通讯作者：
Pramod Kumar, Verma
影响因子：
4.4
作者：
McLaughlin, Kerry A.;Gulati, Kavita;Christie, Michael R.
通讯作者：
Christie, Michael R.