PDF(Pubmed)
Abstract：
BACKGROUND: Metastatic disease is a major and difficult-to-treat complication of lung cancer. Considering insufficient effectiveness of existing therapies and taking into account the current problem of lung cancer chemoresistance, it is necessary to continue the development of new treatments.
METHODS: Previously, we have demonstrated the antitumor effects of reprogrammed CD8+ T-cells (rCD8+ T-cells) from the spleen in mice with orthotopic lung carcinoma. Reprogramming was conducted by inhibiting the MAPK/ERK signalling pathway through MEKi and the immune checkpoint PD-1/PD-L1. Concurrently, CD8+ T-cells were trained in Lewis lung carcinoma (LLC) cells. We suggested that rCD8+ T-cells isolated from the spleen might impede the development of metastatic disease.
RESULTS: The present study has indicated that the reprogramming procedure enhances the survival and cytotoxicity of splenic CD8+ T-cells in LLC culture. In an LLC model of spontaneous metastasis, splenic rCD8 + T-cell therapy augmented the numbers of CD8+ T-cells and CD4+ T-cells in the lungs of mice. These changes can account for the partial reduction of tumors in the lungs and the mitigation of metastatic activity.
CONCLUSIONS: Our proposed reprogramming method enhances the antitumor activity of CD8+ T-cells isolated from the spleen and could be valuable in formulating an approach to treating metastatic disease in patients with lung cancer.
METHODS: Previously, we have demonstrated the antitumor effects of reprogrammed CD8+ T-cells (rCD8+ T-cells) from the spleen in mice with orthotopic lung carcinoma. Reprogramming was conducted by inhibiting the MAPK/ERK signalling pathway through MEKi and the immune checkpoint PD-1/PD-L1. Concurrently, CD8+ T-cells were trained in Lewis lung carcinoma (LLC) cells. We suggested that rCD8+ T-cells isolated from the spleen might impede the development of metastatic disease.
RESULTS: The present study has indicated that the reprogramming procedure enhances the survival and cytotoxicity of splenic CD8+ T-cells in LLC culture. In an LLC model of spontaneous metastasis, splenic rCD8 + T-cell therapy augmented the numbers of CD8+ T-cells and CD4+ T-cells in the lungs of mice. These changes can account for the partial reduction of tumors in the lungs and the mitigation of metastatic activity.
CONCLUSIONS: Our proposed reprogramming method enhances the antitumor activity of CD8+ T-cells isolated from the spleen and could be valuable in formulating an approach to treating metastatic disease in patients with lung cancer.
摘要：
背景：转移性疾病是肺癌的主要且难以治疗的并发症。考虑到现有疗法的有效性不足，并考虑到目前肺癌化疗耐药的问题，有必要继续开发新的治疗方法。
方法：以前，我们已经证明了来自脾脏的重编程CD8+T细胞（rCD8+T细胞）在原位肺癌小鼠中的抗肿瘤作用。通过MEKi和免疫检查点PD-1/PD-L1抑制MAPK/ERK信号通路进行重编程。同时,在Lewis肺癌(LLC)细胞中训练CD8+T细胞。我们建议从脾脏分离的rCD8T细胞可能会阻碍转移性疾病的发展。
结果：本研究表明，重编程程序增强了LLC培养物中脾CD8T细胞的存活和细胞毒性。在自发转移的LLC模型中，脾rCD8+T细胞治疗增加了小鼠肺部CD8+T细胞和CD4+T细胞的数量。这些变化可以解释肺部肿瘤的部分减少和转移活性的缓解。
结论：我们提出的重编程方法增强了从脾脏分离的CD8+T细胞的抗肿瘤活性，在制定治疗肺癌患者转移性疾病的方法中可能是有价值的。
方法：以前，我们已经证明了来自脾脏的重编程CD8+T细胞（rCD8+T细胞）在原位肺癌小鼠中的抗肿瘤作用。通过MEKi和免疫检查点PD-1/PD-L1抑制MAPK/ERK信号通路进行重编程。同时,在Lewis肺癌(LLC)细胞中训练CD8+T细胞。我们建议从脾脏分离的rCD8T细胞可能会阻碍转移性疾病的发展。
结果：本研究表明，重编程程序增强了LLC培养物中脾CD8T细胞的存活和细胞毒性。在自发转移的LLC模型中，脾rCD8+T细胞治疗增加了小鼠肺部CD8+T细胞和CD4+T细胞的数量。这些变化可以解释肺部肿瘤的部分减少和转移活性的缓解。
结论：我们提出的重编程方法增强了从脾脏分离的CD8+T细胞的抗肿瘤活性，在制定治疗肺癌患者转移性疾病的方法中可能是有价值的。
