Seung-hyun Kwon (Veterans Medical Research Institute, Veterans Health Service Medical Center)

Hak Su Kim (Veterans Medical Research Institute, Veterans Health Service Medical Center)

Seung-hyun Kwon (Veterans Medical Research Institute, Veterans Health Service Medical Center)

Taekyu Lim (Division of Hematology-Oncology, Department of Internal Medicine, Veterans Health Service Medical Cente)

Hak Su Kim (Veterans Medical Research Institute, Veterans Health Service Medical Center)

Lung cancer is one of the most common cancers in the world. In particular, non-small cell lung cancer (NSCLC) has a poor prognosis, so the treatment studies are ongoing. Immunotherapy is the most frequently tried treatment (anti-PD1), a multikinase inhibitor drugs (Regorafenib) are also one of the treatments with a good prognosis. Previously we tested the combination effect of using REG and anti-PD1 in lung cancer cell lines. Two non-small cell lung cancer (NSCLC) cell lines (A549, H460) were used to perform REG-induced cytotoxicity and cell survival experiments. When cancer cells were treated with REG, cell viability was decreased and G1/S arrest was confirmed at high doses. We made allogenic mouse model using LLC1 (mouse lung cancer cell) and tested the combination effect of anti-PD1 and REG. We tested the combination effect of anti-PD1 and REG, tumor sizes are significantly decreased on REG and anti-PD1 treated group. And we used nanoLC-ESI-MS/MS to fine proteins that change according to REG and/or anti-PD1 treatment. In the group treated with REG and anti-PD1, it was found that RNA processing related proteins were decreased compared to the control, and cellular metabolic process related proteins were increased. By immunofluorescence, it was confirmed that REG-induced cytotoxic NK cells (Granzyme B) and anti-PD1-induced CD8+ cytotoxic T cells are co-localized and caused an immune response. We propose the possibility of effective cancer treatment by improving the efficacy of immune anticancer drugs used for lung cancer and reducing the side effects that can occur when using high-dose REG. (Funding: RS-2026-25482615)