PD-1 单克隆抗体增强冷冻消融诱导的抗肿瘤免疫反应：乳腺癌小鼠模型研究。

PD-1 monoclonal antibodies enhance the cryoablation-induced antitumor immune response: a breast cancer murine model research.

机构信息

Center for Medical Ultrasound, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.

Department of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

出版信息

Int J Hyperthermia. 2023;40(1):2164625. doi: 10.1080/02656736.2022.2164625.

DOI:10.1080/02656736.2022.2164625

PMID:36966808

Abstract

BACKGROUND

It has been demonstrated that cryoablation (Cryo) causes specific T-cell immune responses in the body; however, it is not sufficient to prevent tumor recurrence and metastasis. In this report, we evaluated changes in the tumor immune microenvironment (TIME) in distant tumor tissues after Cryo and investigated the immunosuppressive mechanisms that limit the efficacy of Cryo.

METHODS

Bilateral mammary tumor models were established in mice, and we first observed the dynamic changes in immune cells and cytokines at different time points after Cryo. Then, we confirmed that the upregulation of PD-1 and PD-L1 signaling in the contralateral tumor tissue was closely related to the immunosuppressive state in the TIME at the later stage after Cryo. Finally, we also evaluated the synergistic antitumor effects of Cryo combined with PD-1 monoclonal antibody (mAb) in the treatment of breast cancer (BC) mouse.

RESULTS

We found that Cryo can stimulate the body's immune response, but it also induces immunosuppression. The elevated PD-1/PD-L1 expression in distant tumor tissues at the later stage after Cryo was closely related to the immunosuppressive state in the TIME but also created the conditions for Cryo combined with PD-1 mAb for BC mouse treatment. Cryo + PD-1 mAb could improve the immunosuppressive state of tumors and enhance the Cryo-induced immune response, thus exerting a synergistic antitumor effect.

CONCLUSIONS

The PD-1/PD-L1 axis plays an important role in suppressing Cryo-induced antitumor immune responses. This study provides a theoretical basis for Cryo combined with PD-1 mAb therapy in clinical BC patients.

摘要

背景

已有研究表明，冷冻消融（Cryo）会在体内引起特定的 T 细胞免疫反应；然而，这不足以预防肿瘤复发和转移。在本报告中，我们评估了 Cryo 后远处肿瘤组织中肿瘤免疫微环境（TIME）的变化，并研究了限制 Cryo 疗效的免疫抑制机制。

方法

在小鼠中建立双侧乳腺肿瘤模型，我们首先观察了 Cryo 后不同时间点免疫细胞和细胞因子的动态变化。然后，我们证实了 Cryo 后晚期对侧肿瘤组织中 PD-1 和 PD-L1 信号的上调与 TIME 中的免疫抑制状态密切相关。最后，我们还评估了 Cryo 联合 PD-1 单克隆抗体（mAb）治疗乳腺癌（BC）小鼠的协同抗肿瘤作用。

结果

我们发现 Cryo 可以刺激机体的免疫反应，但也会诱导免疫抑制。Cryo 后晚期远处肿瘤组织中 PD-1/PD-L1 的表达升高与 TIME 中的免疫抑制状态密切相关，但也为 Cryo 联合 PD-1 mAb 治疗 BC 小鼠创造了条件。Cryo + PD-1 mAb 可以改善肿瘤的免疫抑制状态，增强 Cryo 诱导的免疫反应，从而发挥协同抗肿瘤作用。