Through precise genomic analysis of cancer tissues of patients with non-small cell lung cancer, it is now possible to predict the response of different patients to immunotherapy treatment.
On the 19th, a research team led by Professor Hye-ryun Kim of the Department of Oncology at Yonsei Cancer Hospital, Professor Sung-Yong Park of the Department of Thoracic Surgery at Severance Hospital, and Professor In-Seok Lee and Sang-Jun Ha of Yonsei University College of Life Systems, announced on the 19th that they had discovered an immune cell gene signature that can predict the immune-cancer drug response of EGFR-mutated lung cancer.
The results of this study were published in the latest issue of the international academic journal ‘Nature Communications (IF 14.919)’.
Compared with existing anticancer drugs, immunotherapy has the advantage of showing a high response rate and low side effects and increasing long-term survival rate, so it is used as a standard treatment. However, the limitation is that the treatment response is not uniform and only some patients show good response.
To compensate for this, research is being conducted around the world to reveal the cause of the difference in immune anticancer drug response within the tumor microenvironment of cancer tissue.
The research 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. carried out
As a result of the analysis, in patients with EGFR mutation, B cells, which are immune cells that produce antibodies, CD8 T cells (TRM) that mediate cellular immunity to eliminate cancer cells, and CD4 T cells (TFH) that help B cells produce antibodies appeared to decrease.
In addition, using genomic interaction analysis and multi-immunofluorescence staining analysis in cancer tissue, B cells, CD8 T cells, and CD4 T cell lymphocytes form a tertiary lymphoid structure (TFH-B-TRM network) with each other to form an immune response through local interaction was found to contribute to the promotion of
On the other hand, when dysplasia occurred in the formation of the tertiary lymphoid structure formed by the network between specific immune cells, the response to immunotherapy was low.
The research team analyzed the genetic data of lung cancer patients who received immunotherapy treatment in actual clinical trials using the gene signature that was 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 is expected to be used as a response prediction method that can accurately predict the response of patients with non-small cell lung cancer to immunotherapy. In addition, it is expected to contribute to the development of therapeutic strategies through research to induce a tertiary lymphoid structure composed of the TFH-B-TRM network.
Professor Kim Hye-ryun said, “The gene signature discovered through this study can be used as a response prediction method that can accurately predict the immunotherapy response of patients with non-small cell lung cancer. I hope we can do it,” he said.
Meanwhile, this research was carried out with the support of the National Research Foundation of Korea’s Biomedical Technology Development Next-Generation Applied Omics Project.