In Vitro Study of Cancer Stem Cells and Reprogrammed CD3+CD8+ T Cells: the Search for Personalized Diagnostics and Targeted Treatment of Small Cell Lung Cancer (Experience of a Pilot Study).

The content of cancer stem cells and CD3⁺CD8⁺ T cells in the blood of a patient with small cell lung cancer (SCLC) and chronic obstructive pulmonary disease (COPD) was evaluated. In vitro analysis of tumorospheres allowed us to characterize circulating tumor stem cells in the blood of patients at risk. The fundamental possibility of reprogramming exhausted CD3⁺CD8⁺ T cells (rCD3CD8T) of a patient with SCLC and COPD using a mitogen-activated protein kinase inhibitor (iMEK) and human monoclonal antibody nivolumab was demonstrated. Target cell elimination by rCD3CD8T was achieved by treatment with autologous cancer cell and stem cancer cell lysate in vitro. Thus, blockade of the MAPK/ERK signaling pathway and the PD-1/PD-L1 checkpoints may be used to overcome exhaustion and enhance cytotoxicity of CD3⁺CD8⁺ T cells in patients with SCLC and COPD.