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.
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。