Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yanjiang West Road 107#, Guangzhou, 510120, China.
Genecast Precision Medicine Technology Institute, Beijing, China.
Breast Cancer Res Treat. 2021 Apr;186(3):687-697. doi: 10.1007/s10549-021-06128-4. Epub 2021 Feb 25.
We recently reported results of a phase II trial that camrelizumab plus apatinib induced an objective response rate (ORR) at 43.3% in advanced triple-negative breast cancer (TNBC). This study presents analysis of potential biomarkers.
TILs, CD8 T cells and PD-1/PD-L1 expression were evaluated in tumor samples by immunohistochemistry. 59 Cytokines/chemokines, growth factors, or checkpoint-related proteins, blood immune cell subpopulations were analyzed in blood samples by multiplexed bead immunoassays or flow cytometry. Correlation between biomarkers and clinical outcomes including ORR, progression-free survival (PFS), and overall survival (OS) was analyzed.
28 Patients had biopsies and blood collected. Baseline TILs were significantly associated with longer PFS (P = 0.035). An increase of tumor-infiltrating CD8 T cells > 15% during therapy was associated with higher ORR (P = 0.040). Patients with lower baseline plasma levels of HGF or IL-8 were more likely to respond to treatment (P = 0.005 or 0.001, respectively), and showed a longer PFS and OS. Patients with a decrease of IL-8, or an increase of TIM-3 or CD152 during treatment responded more to treatment (P = 0.008, 0.040, or 0.014, respectively). Responders had a higher baseline CD4 T cells and B cell proportions in blood than non-responders (P = 0.002 and 0.030, respectively).
Higher baseline TILs or a greater increase of tumor-infiltrating CD8 T cells during therapy, lower baseline plasma HGF/IL-8, a decrease of plasma IL-8, an increase of plasma TIM-3/CD152 during therapy, higher baseline CD4 T cells or B cells proportion in blood are potential biomarkers for combinational anti-angiogenesis and immunotherapy in advanced TNBC patients.
我们最近报告了一项 II 期临床试验的结果，卡瑞利珠单抗联合阿帕替尼在晚期三阴性乳腺癌（TNBC）中诱导的客观缓解率（ORR）为 43.3%。本研究分析了潜在的生物标志物。
通过免疫组织化学法评估肿瘤样本中的 TILs、CD8 T 细胞和 PD-1/PD-L1 表达。通过多指标 bead 免疫分析或流式细胞术分析血液样本中的 59 种细胞因子/趋化因子、生长因子或检查点相关蛋白、血液免疫细胞亚群。分析生物标志物与临床结局（包括 ORR、无进展生存期（PFS）和总生存期（OS））之间的相关性。
28 例患者进行了活检和血液采集。基线 TILs 与较长的 PFS 显著相关（P=0.035）。治疗期间肿瘤浸润性 CD8 T 细胞增加>15%与更高的 ORR 相关（P=0.040）。基线时血浆 HGF 或 IL-8 水平较低的患者更有可能对治疗有反应（P=0.005 或 0.001），并且表现出更长的 PFS 和 OS。治疗期间 IL-8 下降或 TIM-3 或 CD152 增加的患者对治疗的反应更明显（P=0.008、0.040 或 0.014）。应答者的基线 CD4 T 细胞和 B 细胞比例高于无应答者（P=0.002 和 0.030）。
较高的基线 TILs 或治疗期间肿瘤浸润性 CD8 T 细胞的增加、较低的基线血浆 HGF/IL-8、治疗期间血浆 IL-8 的下降、血浆 TIM-3/CD152 的增加、较高的基线 CD4 T 细胞或 B 细胞比例血液是晚期 TNBC 患者联合抗血管生成和免疫治疗的潜在生物标志物。
