Dai Mengyan, Tian Zuhong, Xu Fanyuan, Yao Bang, Liang Hongxia, Li Dongyan, Wang Jiangang, Rong Junyan, Liu Tianshuai, Tang Haili, Lu Hongbing, Zhang Wenli
The College of Life Sciences, Northwest University, Xi'an City, 710069, People's Republic of China.
School of Biomedical Engineering, Shaanxi Provincial Key Laboratory of Bioelectromagnetic Detection and Intelligent Perception, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
Breast Cancer (Dove Med Press). 2025 Jun 10;17:483-496. doi: 10.2147/BCTT.S518625. eCollection 2025.
Triple-negative breast cancer (TNBC) is an aggressive malignancy with high metastasis and recurrence rates. Current treatments like chemotherapy and immunotherapy face challenges due to chemotherapy side effects, limited immunotherapy applicability, and TNBC's immunosuppressive microenvironment.
To achieve a more effective treatment for TNBC, a novel therapeutic strategy has been developed, which uses X-ray excited photodynamic therapy (X-PDT) to activate the tumor immune microenvironment following with the immunotherapy of Anti-CTLA4.
Base on the 4T1 tumor mouse model, this study initially investigated the regulatory effects of X-PDT on the tumor immune microenvironment. Subsequently, the therapeutic efficacy of combining X-PDT with Anti-CTLA4 was evaluated for its inhibitory effects on primary, metastatic, and recurrent tumors. The underlying mechanisms were further elucidated through comprehensive techniques including flow cytometry, ELISA, and immunofluorescence assays.
The synergistic strategy can effectively ablate the primary tumor while inhibiting metastasis and preventing recurrence like a vaccine. It enhances intratumoural dendritic cells (DCs) maturation (from 25.7% to 58.3%, < 0.05) and immune T cell infiltration activating a strong anti-tumor immune response. The anti-tumor efficacy of synergistic therapy is enhanced by 2.5 times comparing with immunotherapy alone, while the tumor metastasis has been inhibited significantly. The maturation level of mature dendritic cells was increased from 26.7% to 86.3% ( < 0.01). The intratumoural CD8/CD4 T cells were increased from 0.51% and 1.54% to 15.4% and 23.1% ( < 0.0001), respectively. The synergistic therapy exerts a powerful vaccine-like long-term immune memory function to prevent tumor recurrence with the elevated level of effector memory T (Tem) cells (from 12.8% to 33.3%, < 0.05).
Based on the 4T1 mouse model, developed an effective vaccine-like therapeutic strategy combining X-PDT with Anti-CTLA4, which can effectively ablate tumors, inhibit metastasis, and prevent tumor recurrence. This work may provide a novel effective therapeutic modality for the clinical treatment of TNBC.
三阴性乳腺癌（TNBC）是一种侵袭性恶性肿瘤，具有高转移率和复发率。由于化疗副作用、免疫治疗适用性有限以及TNBC的免疫抑制微环境，目前的化疗和免疫治疗等面临挑战。
为实现对TNBC更有效的治疗，已开发出一种新型治疗策略，即采用X射线激发光动力疗法（X-PDT）激活肿瘤免疫微环境，随后进行抗CTLA4免疫治疗。
基于4T1肿瘤小鼠模型，本研究首先研究了X-PDT对肿瘤免疫微环境的调节作用。随后，评估了X-PDT与抗CTLA4联合治疗对原发性、转移性和复发性肿瘤的抑制作用的治疗效果。通过流式细胞术、酶联免疫吸附测定和免疫荧光测定等综合技术进一步阐明其潜在机制。
这种协同策略能像疫苗一样有效消融原发性肿瘤，同时抑制转移并预防复发。它增强肿瘤内树突状细胞（DCs）成熟（从25.7%增至58.3%，<0.05）以及免疫T细胞浸润，激活强烈的抗肿瘤免疫反应。与单独免疫治疗相比，协同治疗的抗肿瘤疗效提高了2.5倍，同时肿瘤转移得到显著抑制。成熟树突状细胞的成熟水平从26.7%增至86.3%（<0.01）。肿瘤内CD8/CD4 T细胞分别从0.51%和1.54%增至15.4%和23.1%（<0.0001）。协同治疗发挥强大的类似疫苗的长期免疫记忆功能，通过提高效应记忆T（Tem）细胞水平（从12.8%增至33.3%，<0.05）来预防肿瘤复发。
基于4T1小鼠模型，开发出一种将X-PDT与抗CTLA4相结合的有效的类似疫苗的治疗策略，可有效消融肿瘤、抑制转移并预防肿瘤复发。这项工作可能为TNBC的临床治疗提供一种新的有效治疗方式。
