A research team at Severance Hospital has discovered an immune cell gene signature, which can predict the responses of estimated glomerular filtration rate (EGFR)-mutated lung cancer to immunotherapy.
Lung cancer ranks first in the country's cancer mortality rate and occurs either in the lung itself or is caused by metastasis from other organs. Primary lung cancer has two categories -- non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) – with NSCLC accounting for 80 percent of the primary lung cancer cases.
About 50 percent of NSCLC patients in Asia, including Korea, have EGFR mutation.
However, EGFR mutation has a poor response to immunotherapy.
Immunotherapy shows a high response rate and low side effects and increases the long-term survival rate. As a result, hospitals widely use it as a standard treatment. However, it has limits because treatment responses are not uniform, with only some showing good reactions.
Various researches are underway worldwide to reveal the cause of the difference in immunotherapy drug response within the tumor microenvironment of cancer tissue, it added.
The Severance research team, led by Professors Kim Hye-ryun of the Yonsei Cancer Center and Park Seong-yong of the Department of Cardiology, has also been researching this area. Professors Lee In-suk and Ha Sang-jun of the Yonsei University College of Life System also participated in the research.
In discovering the immune cell gene signature that can predict the immune-cancer drug response of EGFR-mutated lung cancer, the team analyzed single-cell transcriptome data to segment immune cells and monitor dynamic changes in the immune cells present in cancer tissues of EGFR mutant lung cancer and EGFR wild-type lung cancer to find out why the response of immunotherapy varies from patient to patient.
The team confirmed that in patients with EGFR mutation, B cells, immune cells that produce antibodies, CD8 T cells, which mediate cellular immunity to eliminate cancer cells, and CD4 T cells, which help B cells produce antibodies, appeared to decrease.
The researchers also confirmed that B cells, CD8 T cells, and CD4 T cell lymphocytes form a tertiary lymphoid structure and enhance the immune response through local interaction using genome interaction analysis and multi-immunofluorescence staining analysis in cancer tissues.
However, when dysplasia occurred in the tertiary lymphoid structure formed by the network between specific immune cells, the response to immunotherapy was low, according to the hospital. Therefore, the team analyzed the genetic data of lung cancer patients who received immunotherapy treatment in actual clinical trials using the gene signature high in EGFR wild-type lung cancer.
As a result of verification, the gene signature showed a high predictive value of the treatment response in lung cancer patients who received immunotherapy treatment.
“The gene signature discovered through this study will help hospitals conduct a response prediction method that can accurately predict the response of NSCLC patients to immunotherapy,” Professor Kim said. "We expect to provide improved immunotherapy for cancer patients in the future."