晚期转移性癌症中纳武单抗联合伊匹单抗的反应和耐药性的免疫学特征。
Immunologic signatures of response and resistance to nivolumab with ipilimumab in advanced metastatic cancer.
发表日期：2024 Oct 07
作者：
Apostolia M Tsimberidou, Farah A Alayli, Kwame Okrah, Alexandra Drakaki, Danny N Khalil, Shivaani Kummar, Saad A Khan, F Stephen Hodi, David Y Oh, Christopher R Cabanski, Shikha Gautam, Stefanie L Meier, Meelad Amouzgar, Shannon M Pfeiffer, Robin Kageyama, EnJun Yang, Marko Spasic, Michael T Tetzlaff, Wai Chin Foo, Travis J Hollmann, Yanyun Li, Matthew Adamow, Phillip Wong, Jonni S Moore, Sharlene Velichko, Richard O Chen, Dinesh Kumar, Samantha Bucktrout, Ramy Ibrahim, Ute Dugan, Lisa Salvador, Vanessa M Hubbard-Lucey, Jill O'Donnell-Tormey, Sandra Santulli-Marotto, Lisa H Butterfield, Diane M Da Silva, Justin Fairchild, Theresa M LaVallee, Lacey J Padrón, Padmanee Sharma
来源：
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要：
迫切需要识别预测免疫检查点抑制剂（ICI）反应的泛肿瘤生物标志物。在 AMADEUS 临床试验 (NCT03651271) 中，评估了各种晚期实体瘤患者的瘤内 CD8 百分比的变化及其对 ICI 的反应。根据肿瘤 CD8 水平对患者进行分组：CD8 <15%（CD8-低）的患者接受纳武单抗（抗 PD-1）加伊匹单抗（抗 CTLA4），CD8 ≥15%（CD8-高）的患者接受纳武单抗单一疗法。 79 名患者（72 名 CD8 低和 7 名 CD8 高）接受了治疗。 CD8低的疾病控制率为25.0%（18/72；95% CI：15.8-35.2），CD8高的疾病控制率为14.3%（1/7；95% CI：1.1-43.8）。 35.9% (14/39; 95% CI: 21.8-51.4) 的患者肿瘤从治疗前 CD8 <15% 转变为治疗后 ≥15%。多组学分析表明，CD8 低反应者具有炎症性肿瘤微环境预处理，并且治疗后 CD8 T 细胞、CD4 T 细胞、B 细胞和巨噬细胞的涌入增强了这种微环境。这些发现揭示了转移性疾病患者 ICI 反应的关键泛癌免疫学特征。© 2024 Tsimberidou 等人。
Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8 <15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) and those with CD8 ≥15% (CD8-high) received nivolumab monotherapy. 79 patients (72 CD8-low and 7 CD8-high) were treated. The disease control rate was 25.0% (18/72; 95% CI: 15.8-35.2) in CD8-low and 14.3% (1/7; 95% CI: 1.1-43.8) in CD8-high. Tumors from 35.9% (14/39; 95% CI: 21.8-51.4) of patients converted from CD8 <15% pretreatment to ≥15% after treatment. Multiomic analyses showed that CD8-low responders had an inflammatory tumor microenvironment pretreatment, enhanced by an influx of CD8 T cells, CD4 T cells, B cells, and macrophages upon treatment. These findings reveal crucial pan-cancer immunological features for ICI response in patients with metastatic disease.© 2024 Tsimberidou et al.