术前单次使用卡瑞利珠单抗联合微波消融治疗早期乳腺癌的探索性研究。

Preoperative single-dose camrelizumab and/or microwave ablation in women with early-stage breast cancer: A window-of-opportunity trial.

机构信息

Department of Breast Surgery & General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention, and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

Pancreas Center & Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute of Nanjing Medical University, Nanjing 210029, China.

出版信息

Med. 2024 Apr 12;5(4):291-310.e5. doi: 10.1016/j.medj.2024.01.015. Epub 2024 Feb 27.

DOI:10.1016/j.medj.2024.01.015

PMID:38417440

Abstract

BACKGROUND

Immune checkpoint blockade has shown low response rates for advanced breast cancer, and combination strategies are needed. Microwave ablation (MWA) may be a trigger of antitumor immunity. This window-of-opportunity trial (ClinicalTrials.gov: NCT04805736) was conducted to determine the safety and feasibility of preoperative camrelizumab (an anti-PD-1 antibody) combined with MWA in the treatment of early-stage breast cancer.

METHODS

Sixty participants were randomized to preoperatively receive single-dose camrelizumab alone (n = 20), MWA alone (n = 20), or camrelizumab+MWA (n = 20). A random number table was used to allocate interventions. The primary outcome was the safety and feasibility of MWA combined with camrelizumab.

FINDINGS

Camrelizumab and MWA were well tolerated alone and in combination without delays in prescheduled surgery. No treatment-related grade III/IV adverse events were observed. Different from in the single-dose camrelizumab or MWA group, participants showed stable counts of blood cells after combination therapy. After combination therapy, peripheral CD8 T cells showed enhanced cytotoxic and effect-memory functions. Clonal expansional CD8 T cells showed higher cytotoxic activity and effector memory- and tumor-specific signatures than emergent clones after combination therapy. Enhanced interactions between clonal expansional CD8 T cells and monocytes were observed, suggesting that monocytes contributed to the enhanced functions of clonal expansional CD8 T cells. Major histocompatibility complex (MHC) class I-related pathways and interferon signaling pathways were activated in monocytes by combination therapy.

CONCLUSIONS

Camrelizumab combined with MWA was feasible for early-stage breast cancer. Peripheral CD8 T cells were activated after combination therapy, dependent on monocytes with activated MHC class I pathways.

FUNDING

This study was supported by the Natural Science Foundation of Jiangsu Province (BK20230017).

摘要

背景

免疫检查点阻断在晚期乳腺癌中的反应率较低，需要联合策略。微波消融（MWA）可能是触发抗肿瘤免疫的因素。这项机会性试验（ClinicalTrials.gov：NCT04805736）旨在确定术前卡瑞利珠单抗（一种抗 PD-1 抗体）联合 MWA 治疗早期乳腺癌的安全性和可行性。

方法

60 名参与者被随机分为三组，分别接受单剂量卡瑞利珠单抗单独治疗（n=20）、MWA 单独治疗（n=20）或卡瑞利珠单抗+MWA 联合治疗（n=20）。采用随机数字表分配干预措施。主要结局是 MWA 联合卡瑞利珠单抗的安全性和可行性。

结果

卡瑞利珠单抗和 MWA 单独使用或联合使用均耐受良好，且不会延迟预定的手术。未观察到与治疗相关的 III/IV 级不良事件。与单剂量卡瑞利珠单抗或 MWA 组不同，联合治疗后参与者的血细胞计数稳定。联合治疗后，外周血 CD8 T 细胞表现出增强的细胞毒性和效应记忆功能。与联合治疗后出现的新克隆相比，克隆扩增的 CD8 T 细胞表现出更高的细胞毒性活性和效应记忆及肿瘤特异性特征。观察到克隆扩增的 CD8 T 细胞与单核细胞之间的相互作用增强，提示单核细胞有助于增强克隆扩增的 CD8 T 细胞的功能。MHC Ⅰ类相关途径和干扰素信号途径在单核细胞中被联合治疗激活。