工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
TIL（肿瘤浸润淋巴细胞）PD-1 表达预测抗 PD-1/PD-L1 免疫治疗应答
英文原题：Tumor Infiltrating Lymphocyte Expression of PD-1 Predicts Response to Anti-PD-1/PD-L1 Immunotherapy.
查看英文原题
Tumor Infiltrating Lymphocyte Expression of PD-1 Predicts Response to Anti-PD-1/PD-L1 Immunotherapy.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
肿瘤中 TIL-PD-1 阳性（1%）与 ICB 后显著更长的无进展生存期和总生存期相关。ClinicalTrials.gov ID: NCT02478931。
研究思路结论见上方概要
背景
许多研究关注程序性死亡受体配体1（PD-L1）表达在预测免疫治疗结局中的作用。关于表达程序性死亡受体1（PD-1；PD-L1的受体）的TIL（肿瘤浸润淋巴细胞）（TILs）在PD-1/PD-L1抗体反应性中的作用，临床数据有限。然而，临床前研究表明，表达PD-1的TILs有助于肿瘤免疫逃逸。
方法
本研究分析了TIL-PD-1状态与免疫检查点阻断（ICB）治疗后结局之间的关联。我们评估了123例接受靶向PD-1/PD-L1信号轴单克隆抗体治疗的各种实体瘤患者。此外，还评估了8706份实体瘤标本的TIL-PD-1和肿瘤突变负荷（TMB）状态。
结果
肿瘤中存在表达 PD-1 的 TIL 与 ICB 治疗后中位无进展生存期（7.0 vs 1.9 个月；p = 0.006）和总生存期（18.1 vs 8.0 个月；p = 0.04）延长相关。TIL-PD-1 阳性患者的客观缓解率（ORR）为 41%（95% CI，24-61；N = 12/29），而 TIL-PD-1 阴性患者为 17%（95% CI，4-43；N = 3/17）（p = 0.18）。作为连续变量分析时，TIL-PD-1 与 TMB 在 8706 份实体瘤样本中显示弱相关（Pearson r = 0.074）；作为分类变量分析时（截断值：TIL-PD-1 1% 和 TMB 10 mutations/Mb），这两个变量相关（p < 0.0001）。TIL-PD-1 阳性状态还与若干基因内病理性变异的富集相关，最显著的是 TP53（校正 p < 0.05）。
展开英文摘要原文
METHODS
This study analyzed the association between TIL-PD-1 status and outcome after immune checkpoint blockade (ICB) therapy. We evaluated 123 patients with various solid tumors treated with monoclonal antibodies targeting the PD-1/PD-L1 signaling axis. Additionally, 8706 solid tumor specimens were assessed for TIL-PD-1 and tumor mutational burden (TMB) status.
RESULTS
The presence of PD-1-expressing TILs in tumors was associated with increased median progression-free survival (7.0 vs 1.9 months; p = 0.006) and overall survival (18.1 vs 8.0 months; p = 0.04) after treatment with ICB. TIL-PD-1-positive patients had an objective response rate (ORR) of 41% (95% CI, 24-61; N = 12/29) compared with 17% (95% CI, 4-43; N = 3/17) for TIL-PD-1-negative patients ( p = 0.18). Analyzed as continuous variables, TIL-PD-1 and TMB showed a weak correlation in 8706 solid tumor samples (Pearson r = 0.074); when analyzed as categorical variables (cutoffs: TIL-PD-1 1% and TMB 10 mutations/Mb), the two variables are correlated ( p < 0.0001). TIL-PD-1-positive status is also associated with enrichment of pathologic variants within several genes, most notably TP53 (adjusted p < 0.05).
CONCLUSION
TIL-PD-1 positivity in tumors ( 1%) is associated with significantly longer progression-free and overall survival after ICB. ClinicalTrials.gov ID: NCT02478931 .
论文信息
- 作者
- Bevins NJ、Okamura R、Montesion M、Adashek JJ、Goodman AM、Kurzrock R
- 第一作者单位
- Department of Pathology, University of California San Diego, San Diego, CA USA.United States
- 通讯作者单位
- Center for Personalized Cancer Therapy, Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, San Diego, CA, USA.United States
- 期刊
- Journal of immunotherapy and precision oncology2022 Nov
- 原文标识
- PubMed 36483582 · DOI 10.36401/JIPO-22-9
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →