Xu Fengkuo, Sang Jing, Wang Nan, Wang Meixiang, Huang Yahan, Ma Ji, Chen Huanan, Xie Qi, Wei Zhigang, Ye Xin
Department of Oncology, Lung Cancer Center, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, 250014, China.
Department of Pathology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, Shandong, China.
Cancer Immunol Immunother. 2025 Mar 25;74(5):161. doi: 10.1007/s00262-025-04003-5.
Microwave ablation (MWA) is a super minimally invasive therapeutic approach that has been widely applied in the treatment of non-small cell lung cancer (NSCLC). Although MWA can elicit antitumor immune responses, these immune responses are not relatively steady and insufficient to completely clear recurrence tumor cells within the body. Immunotherapy monotherapy has shown low clinical efficacy in the treatment of advanced NSCLC. MWA combined with immune checkpoint inhibitors (ICIs) is a promising therapeutic approach. However, the mechanism of synergic effect remains elusive. In this study, we have conducted a retrospective analysis of the clinical outcomes of MWA combined with ICIs, finding that the combinational therapy yielded superior Objective Response Rate and longer Progression-Free Survival. In preclinical models, we established a tumor rechallenged model to address post-MWA recurrence and to delve into the underlying mechanisms of the combined therapy. We observed that the combined treatment (MWA + PD-L1 blockade therapy) effectively addressed the issue of tumor recurrence in tumor rechallenged model. The combinational therapy increased the function and percentage of CD8 tumor-infiltrating lymphocytes, enhanced the functionality of CD8 T cells within tumor-draining lymph nodes (TdLNs), and elevated the proportion of T central memory cells. Additionally, the combined treatments promoted the proportion of Migration Dendritic Cells type 1 (Mig DC1) within TdLNs, thereby enhancing their activation potential. Notably, FTY720-mediated blockade of lymphocyte egress abolished the therapeutic benefits, confirming TdLNs-dependent systemic immunity. Moreover, the efficacy of the combinational therapy depended on the migration of T cells from TdLNs to tumor site. In summary, we proposed a potentially effective combined treatment regimen and have elucidated the underlying cellular mechanisms that underpin its efficacy.
微波消融（MWA）是一种超微创治疗方法，已广泛应用于非小细胞肺癌（NSCLC）的治疗。虽然MWA可引发抗肿瘤免疫反应，但这些免疫反应不太稳定，不足以完全清除体内的复发肿瘤细胞。免疫疗法单药治疗在晚期NSCLC的治疗中显示出较低的临床疗效。MWA联合免疫检查点抑制剂（ICI）是一种有前景的治疗方法。然而，协同作用的机制仍不清楚。在本研究中，我们对MWA联合ICI的临床结果进行了回顾性分析，发现联合治疗产生了更高的客观缓解率和更长的无进展生存期。在临床前模型中，我们建立了肿瘤再激发模型，以解决MWA后的复发问题，并深入探究联合治疗的潜在机制。我们观察到联合治疗（MWA + PD-L1阻断疗法）有效地解决了肿瘤再激发模型中的肿瘤复发问题。联合治疗增加了CD8肿瘤浸润淋巴细胞的功能和百分比，增强了肿瘤引流淋巴结（TdLNs）内CD8 T细胞的功能，并提高了T中央记忆细胞的比例。此外，联合治疗促进了TdLNs内1型迁移树突状细胞（Mig DC1）的比例，从而增强了它们的激活潜力。值得注意的是，FTY720介导的淋巴细胞流出阻断消除了治疗效果，证实了依赖TdLNs的全身免疫。此外，联合治疗的疗效取决于T细胞从TdLNs迁移到肿瘤部位。总之，我们提出了一种潜在有效的联合治疗方案，并阐明了其疗效背后的细胞机制。
