免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:From Immunobiology to Clinical Application: Tumor-Infiltrating Lymphocytes in Melanoma.
From Immunobiology to Clinical Application: Tumor-Infiltrating Lymphocytes in Melanoma.
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TIL(肿瘤浸润淋巴细胞)(TILs)在针对黑色素瘤的免疫反应中发挥关键作用。它们既是活跃肿瘤环境的标志物,也是过继细胞治疗中的治疗手段。本叙述性综述涵盖了目前对TIL生物学、其预后和预测价值,以及TIL过继细胞治疗(TIL-ACT)在晚期黑色素瘤中应用的认识。
我们检索了PubMed/MEDLINE、Web of Science和ClinicalTrials.gov,截止至2026年1月,使用与黑色素瘤、TILs、过继细胞治疗、免疫检查点抑制剂、新抗原、T细胞受体克隆性和空间转录组学相关的术语。我们纳入了原始研究、重大临床试验、转化研究和关键综述。
黑色素瘤通常具有许多新抗原,这导致肿瘤内TILs数量较高。这些TILs、其排列方式以及它们与髓系细胞的相互作用影响其抗肿瘤效果。通过显微镜和其他检测观察到的TILs特征有助于预测患者结局,甚至在治疗前即可预测。研究表明,TIL-ACT在约30-50%对免疫检查点抑制剂无应答的黑色素瘤患者中产生客观缓解。部分患者实现持久的完全缓解,尽管该治疗可导致显著的、多为短期的副作用,源于淋巴细胞清除和白细胞介素-2。新研究指出与患者、肿瘤和TIL产品相关的因素影响治疗成功,支持使用生物标志物和联合策略。
基于TIL的过继细胞治疗现已成为抗PD-1治疗失败后晚期黑色素瘤的一种有前景的个性化治疗方法。未来的研究应侧重于识别可靠的生物标志物、改进 TIL 产品、联合治疗以改变肿瘤环境,以及提高生产效率,以确保更多患者能够安全地获得 TIL 治疗。
Background: Tumor-infiltrating lymphocytes (TILs) play a key role in the immune response against melanoma. They act as both markers of an active tumor environment and as treatments in adoptive cell therapy. This narrative review covers what is currently known about TIL biology, their prognostic and predictive value, and the use of TIL-based adoptive cell therapy (TIL-ACT) in advanced melanoma.
Methods: We searched PubMed/MEDLINE, Web of Science and clinicaltrials. gov through January 2026 using terms related to melanoma, TILs, adoptive cell therapy, immune checkpoint inhibitors, neoantigens, T-cell receptor clonality, and spatial transcriptomics.
We included original research, major clinical trials, translational studies and key reviews. Results: Melanoma often has many neoantigens, which leads to a high number of tumor-resident TILs. These TILs, their arrangement, and their interactions with myeloid cells influence how well they fight tumors. Features of TILs seen under the microscope and through other tests can help predict patient outcomes, even before treatment. Studies show that TIL-ACT leads to objective responses in about 30-50% of patients whose melanoma did not respond to immune checkpoint inhibitors.
Some patients achieve lasting complete remissions, though the treatment can cause significant, mostly short-term side effects from lymphodepletion and interleukin-2. New research points to factors related to the patient, tumor, and TIL product that affect treatment success, supporting the use of biomarkers and combination strategies.
Conclusions: TIL-based adoptive cell therapy is now a promising, personalized treatment for advanced melanoma after anti-PD-1 therapy has failed. Future studies should focus on identifying reliable biomarkers, improving TIL products, combining therapies to change the tumor environment, and making manufacturing more efficient to ensure more patients can safely access TIL therapy.
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