A recent study has identified a specific genetic mutation pattern that may enhance the effectiveness of immunotherapy in pancreatic cancer, which has generally shown limited response compared to other cancers.

▲(From left) Professor Eunsung Jun of the Biomedical Research Center and Professor Song Cheol Kim of the Division of Hepatobiliary and Pancreatic Surgery

The research team, led by Professor Eunsung Jun of the Biomedical Research Center and Professor Song Cheol Kim of the Division of Hepatobiliary and Pancreatic Surgery at Asan Medical Center, reported that a higher presence of immune cells in the tumor microenvironment significantly improves survival in pancreatic cancer patients. They also found that the distribution of immune cells is closely associated with specific subtypes of KRAS (Kristen Rat Sarcoma viral oncogene homolog) mutations, which is a major driver mutation in pancreatic cancer.

To analyze the tumor microenvironment of pancreatic cancer, the research team conducted multiplex immunohistochemistry on tumor tissues from 17 patients who had undergone surgery. The results showed that immune cells were approximately 3.8 times more prevalent in the extracellular matrix (ECM), which accumulates around cancer cells and contributes to treatment resistance, than in the tumor site. Notably, a higher abundance of T cells was associated with significantly improved survival. While T cell numbers increased in proportion to ECM deposition, a sharp decline in T cell presence was observed when ECM density exceeded approximately 40%.

The research team also conducted whole-exome sequencing to analyze the genetic profiles of the tumors and found that the observed differences in T cell distribution were influenced by specific genetic mutations in pancreatic cancer. In particular, the team observed that among subtypes of the KRAS mutation, which is a key driver of pancreatic cancer, tumors with the G12V variant showed more active T cell infiltration compared to those with the G12D variant. Moreover, using patient-derived tumor organoid models engineered with KRAS mutations, the team identified factors associated with reduced T cell activity.

This study was supported by the Ministry of Science and ICT and the Ministry of Health and Welfare, which was recently published in the international oncology journal ‘Cancer Letters.’