一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Microwave ablation combined with dendritic cells enhances CD8(+) T cell activation in rechallenged tumor mouse model.
Microwave ablation combined with dendritic cells enhances CD8(+) T cell activation in rechallenged tumor mouse model.
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我们的研究结果揭示了 MWA 与基于 DC 的治疗通过 cDC1 激活和 CD8⁺ T 细胞增强发挥协同抗肿瘤机制,为减少 MWA 术后肿瘤复发提供了一种有前景的策略。
微波消融(MWA)在非小细胞肺癌(NSCLC)患者中已显示出良好的安全性和有效性。然而,局部复发仍是影响长期生存的主要问题。树突状细胞(DCs)功能障碍是限制有效T细胞介导抗肿瘤反应的关键免疫抑制因素。为克服这一局限,我们评估了MWA联合DC免疫治疗的潜在疗效。
建立Lewis肺癌(LLC)再攻击小鼠模型,以评估MWA与DC治疗联合预防消融后肿瘤复发的疗效。通过流式细胞术分析肿瘤及肿瘤引流淋巴结(TdLNs)中的免疫格局。
MWA与DC治疗的联合显著抑制了肿瘤复发并促进了强效抗肿瘤免疫,表现为复发肿瘤和TdLNs中CD8⁺ T细胞比例增加及功能活化。此外,联合治疗大幅提高了TdLNs内迁移型1型经典树突状细胞(Mig cDC1s)的频率和免疫刺激能力。这些结果表明,cDC1s是MWA联合DC治疗所诱导的增强抗肿瘤反应的关键介质。
Microwave ablation (MWA) has shown favorable safety and efficacy in patients with non-small cell lung cancer (NSCLC). However, local recurrence remains a major concern that compromises long-term survival. Dysfunction of dendritic cells (DCs) constitutes a key immunosuppressive factor that limits effective T cell-mediated antitumor responses. To overcome this limitation, we evaluated the therapeutic potential of combining MWA with DC-based immunotherapy.
A Lewis lung carcinoma (LLC) rechallenge mouse model was established to assess the efficacy of the combination of MWA and DC therapy in preventing post-ablation tumor recurrence. The immune landscape in tumors and tumor-draining lymph nodes (TdLNs) was analyzed by flow cytometry.
The combination of MWA and DC therapy markedly suppressed tumor recurrence and promoted potent antitumor immunity, as evidenced by an increased proportion and functional activation of CD8⁺ T cells in both recurrent tumors and TdLNs. In addition, the combination treatment substantially increased the frequency and immunostimulatory capacity of migratory type 1 conventional dendritic cells (Mig cDC1s) within TdLNs. These results indicate that cDC1s are crucial mediators of the enhanced antitumor response induced by MWA combined with DC therapy.
Our findings highlight a synergistic antitumor mechanism of MWA and DC-based therapy through cDC1 activation and CD8⁺ T cell enhancement, providing a promising strategy to reduce tumor recurrence after MWA.
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