Consequences of Reprogrammed CD8+ T-Cell Therapy for Lewis Lung Carcinoma Cells and Neovasculogenesis in C57BL/6 Mice.

Abstract

We studied the effect of reprogrammed CD8⁺ T cells (rT cells) from the bone marrow of intact mice on tumor cells and neovasculogenesis in mice with orthotopic Lewis lung carcinoma (LLC). Reprogramming of T cells was carried out using a MEK inhibitor and a PD-1 blocker; the targeting of rT cells to tumor cells was achieved by preincubation with LLC cell lysate. It was shown that the antitumor effect of rT cells was based on apoptosis of tumor cells. In addition, cell therapy reduced the number of endothelial cells (CD45^-CD309⁺) and angiogenic cell precursors (CD45^-CD117⁺CD309⁺), mesenchymal stem cells (CD45^-CD31^-CD34^-CD44⁺), myeloid (CD45⁺CD34⁺CD31^-) and non-myeloid (CD45⁺CD34^-CD31^-) fibrocytes, and leukocytes (CD45⁺) in the lungs and increased their number in the blood. Thus, rT cells impaired the recruitment of neovasculogenic cells to the lung. The antitumor effects of rT cells are superior to those of naive CD8⁺ T cells. The proposed reprogramming method can be useful in developing effective approaches to the therapy of lung cancer, as it allows obtaining cytotoxic rT cells capable of reducing the activity of neovasculogenesis.