Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
J Exp Med. 2024 Oct 7;221(10). doi: 10.1084/jem.20240152. Epub 2024 Aug 27.
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.
鉴定预测免疫检查点抑制剂（ICI）反应的泛肿瘤生物标志物至关重要。在 AMADEUS 临床试验（NCT03651271）中，对各种晚期实体瘤患者的肿瘤内 CD8 百分比变化及其对 ICI 的反应进行了评估。根据肿瘤 CD8 水平对患者进行分组：CD8<15%（CD8-低）的患者接受纳武利尤单抗（抗 PD-1）联合伊匹单抗（抗 CTLA4），CD8≥15%（CD8-高）的患者接受纳武利尤单抗单药治疗。共治疗了 79 名患者（72 名 CD8-低和 7 名 CD8-高）。CD8-低患者的疾病控制率为 25.0%（18/72；95%CI：15.8-35.2），CD8-高患者为 14.3%（1/7；95%CI：1.1-43.8）。35.9%（14/39；95%CI：21.8-51.4）的患者的肿瘤从治疗前 CD8<15%转化为治疗后≥15%。多组学分析显示，CD8-低应答者在治疗前具有炎症性肿瘤微环境，在治疗后 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对 ICI 反应的关键泛癌免疫学特征。
