Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia.
Goldberg ED Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Centre of the Russian Academy of Sciences, Lenin, 3, 634028, Tomsk, Russia.
BMC Cancer. 2024 Apr 25;24(1):522. doi: 10.1186/s12885-024-12203-y.
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.
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.
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.
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.
转移性疾病是肺癌的一种主要且难以治疗的并发症。鉴于现有疗法效果不足，并考虑到当前肺癌化疗耐药的问题，有必要继续开发新的治疗方法。
我们之前已经证明了在患有原位肺癌的小鼠中，来自脾脏的重编程 CD8 T 细胞（rCD8 T 细胞）具有抗肿瘤作用。通过 MEKi 和免疫检查点 PD-1/PD-L1 抑制 MAPK/ERK 信号通路来进行重编程。同时，将 CD8 T 细胞在 Lewis 肺癌（LLC）细胞中进行训练。我们提出，从脾脏分离出的 rCD8 T 细胞可能会阻碍转移性疾病的发展。
本研究表明，重编程程序增强了 LLC 培养物中脾脏 CD8 T 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的 CD8 T 细胞和 CD4 T 细胞数量。这些变化可以部分解释肺部肿瘤的减少和转移活性的减轻。
我们提出的重编程方法增强了从脾脏分离出的 CD8 T 细胞的抗肿瘤活性，对于制定治疗肺癌患者转移性疾病的方法可能具有重要价值。
