A team led by Jong-seok Lim, a professor in the Division of Biological Sciences, has identified the MITF gene as a novel regulator of the differentiation and immunosuppressive function of myeloid-derived suppressor cells in breast and lung cancer.

(From left) Professor Jong-seok Lim, Division of Biological Sciences, and Researcher Ah-ram Lee

According to the research team, myeloid-derived suppressor cells are cells that fail to differentiate in response to various stimuli and remain immunosuppressive, leading to cancer progression. In particular, in the tumor microenvironment, myeloid-derived suppressor cells inhibit the activity of T cells, leading to resistance to anti-cancer drugs and ultimately contributing to the poor prognosis of cancer patients.

Recently, there has been a lot of research on combination therapies that target myeloid-derived suppressor cells to suppress resistance to cancer drugs. However, markers to select for myeloid-derived suppressor cells in mice or humans were still unclear, and effectively targeting myeloid-derived suppressor cells remained a challenge.

The research team found that as breast and lung cancer progress in mice, MITF e-x-p-r-e-s-s-i-o-n increases in myeloid-derived suppressor cells specifically compared to other myeloid cells, and that MITF gene regulation can alter the differentiation and activity of myeloid-derived suppressor cells.

The research team validated the tumor suppression and increased T cell activity by MITF inhibition of myeloid-derived suppressor cells in animal models. By observing an increased number of MITF-positive myeloid-derived suppressor cells in cancer tissues of lung and head and neck cancer patients compared to lymph nodes, they predicted that the e-x-p-r-e-s-s-i-o-n of MITF might play an important role in myeloid-derived suppressor cells in cancer patients as well as in animal models.

Schematic illustrating that MITF e-x-p-r-e-s-s-i-o-n on myeloid-derived suppressor cells in the tumor microenvironment is involved in suppressing T cell activity

The significance of this study is that they observed the e-x-p-r-e-s-s-i-o-n of MITF, which is not well known in immune cells, and suggested MITF as a new biomarker to target myeloid-derived suppressor cells. These observations are expected to contribute significantly to the development of new therapeutics, especially those that can be used in combination with immuno-oncology drugs.

"By developing small molecules that target MITF in the future, we expect to achieve the goal of developing a new class of drugs that increase the efficacy of immuno-oncology drugs, expand their indications, or reduce their side effects," said Professor Jong-seok Lim.

The findings were published on January 10 in the Journal for ImmunoTherapy of Cancer (IF=12.485), one of the top journals in the field of cancer immunotherapy.

(Title of Paper: Novel role of microphthalmia-associated transcription factor in modulating the differentiation and immunosuppressive functions of myeloid-derived suppressor cells)