Reprogrammed CD8⁺ T-Cells Isolated from the Mouse Spleen Increase the Number of Immune Cells with Antitumor Activity and Decrease the Amount of Cancer Stem Cells

Abstract

We have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). In the orthotopic LLC model, cell therapy with rsCD8+T-cells increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung tissue from mice. The amount of cancer stem cells (CSC) decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

Keywords

• reprogrammed spleen CD8⁺ T-cells
• Lewis lung carcinoma
• cancer stem cell
• CD8⁺ and CD4⁺ T-cells
• antimetastatic activity