γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
我们的发现表明,活化的γδ T细胞可能是SCLC治疗的有价值靶点。
英文原题:Successful ex vivo expansion of tumor infiltrating lymphocytes with systemic chemotherapy prior to surgical resection.
这些肿瘤的TILs在体外扩增后平均达到2.1E8(总存活淋巴细胞计数),总体成功率为90.9%。
TIL(肿瘤浸润淋巴细胞)已在多种实体瘤患者中展现出有效的临床结局,包括黑色素瘤、胃肠道肿瘤、肺癌和头颈癌。目前,大多数临床试验要求患者在肿瘤组织切除前未接受过系统性治疗,以避免化疗对离体TIL扩增的干扰。该策略的主要缺点在于限制了许多符合条件的癌症患者获得TIL治疗的机会。过去十年间,T细胞离体扩增技术取得了实质性进展。在本研究中,我们探讨了纳入在手术切除前接受过化疗的患者的可能性。我们收集了17例初治病例的肿瘤组织,以及5例接受过化疗病例的肿瘤组织。本研究纳入的癌症适应症为结直肠癌和肺癌,来源于原发灶和转移灶,如肝脏和脑。这些肿瘤来源的TIL经离体扩增后平均达到2.1E8(总活淋巴细胞计数),总体成功率为90.9%。随后,分别使用流式细胞术和ELISA分析TIL表型和细胞因子产生。我们证明,尽管在手术切除前接受过化疗,仍可从肿瘤组织中扩增出功能性TIL。我们观察到接受化疗与未接受化疗组之间在表型或功能上无显著差异。无论切除前是否接受过化疗,TIL扩增速率和特征均相似,从而为在TIL治疗试验中招募具有最近化疗史的患者提供了可能性。
Tumor infiltrating lymphocytes (TIL) have demonstrated efficacious clinical outcomes for many patients with various types of solid cancers, including melanoma, gastrointestinal cancer, lung cancer, and head and neck cancer. Currently, the majority of clinical trials require that patients did not receive systemic therapy right before tumor tissue resection to avoid the interference of chemotherapy in the ex vivo TIL expansion. The primary disadvantage of this strategy is limiting the accessibility of TIL therapy for many eligible cancer patients. Over the past decade, substantial progress has been made for ex vivo expansion technologies in T cells. In this study, we investigated the possibility of enrolling patients who underwent chemotherapy prior to surgical resection. We collected seventeen tumor tissues from treatment naive cases, and five from cases that underwent chemotherapies. Cancer indications enrolled in this study were colorectal and lung cancers from both primary and metastatic sites, such as liver and brain. TILs from these tumors were expanded ex vivo to 2.1E8 (total viable lymphocytes counts) on average, with an overall success rate of 90.9%. Subsequently, TIL phenotypes and cytokine production were analyzed using flow cytometry and ELISA, respectively. We demonstrated functional TIL expansion from tumor tissues despite chemotherapy prior to surgical resection. We observed no significant phenotypic or functional differences between groups with and without chemotherapy. TIL expansion rate and characteristics were similar regardless of chemotherapy prior to resection, thereby providing a possibility to recruit patients with the most recent chemotherapy history in TIL therapy trials.
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