A local joint research team has found that a combination of programmed cell death protein 1 (PD-1) inhibitor and 4-1BB agonist significantly reinvigorates exhausted CD8 T cells in patients with metastatic ovarian cancer.
The research team, led by Professors Park Su-hyung of the Graduate School of Medical Science and Engineering at Korea Advanced Institute of Science and Technology (KAIST) and Lee Jung-yun at Severance Hospital, identified tumor-specific immune cells' characteristics and suggested a new way to treat cancer with immuno-cancer drugs.
CD8 T cells can mount an adaptive immune response to kill cancer cells.
Tumor creates a microenvironment that reduces CD8 T cells' function, making it difficult for doctors to kill the cancer cells. It induces an increase in the expression of immune checkpoint receptors such as PD-1 and inhibits CD8 T cells. Immune checkpoint inhibitors show high therapeutic effects in malignant melanoma, non-small cell lung cancer, and kidney cancer, but the success rate is less than 20 percent in most solid cancers.
To find a treatment that can overcome it, researchers focused on the characteristics of tumor-specific T cells among CD8 T cells mixed in the metastatic sites of ovarian cancer.
The joint research team found that the more the expression of PD-1 receptors, the lower the CD8 T cells' function becomes. However, researchers also confirmed that the expression of 4-1BB, a type of costimulatory receptor that enhances immunity, increased.
"This study has significance in providing the basis for customized medicine by identifying the heterogeneity of exhausted CD8 T cells in the microenvironment of ovarian cancer and presenting immunological characteristics of CD8 T cells at primary and metastatic sites for the first time," KAIST Professor Park said.
Severance Professor Lee Jung-yun also said, "The study results propose a new therapeutic option for metastatic ovarian cancer, where immunotherapy has shown poor performance, and we expect to confirm the efficacy through clinical trials that can help patients in the future."
The study, "4-1BB Co-stimulation Further Enhances Anti-PD-1-Mediated Reinvigoration of Exhausted CD39+ CD8 T Cells from Primary and Metastatic sites of Epithelial Ovarian Cancers," was published in the latest issue of the Journal for ImmunoTherapy of Cancer.