T cells are important immune cells that patrol the body and protect us from infection and cancer. Many solid tumors have evolved strategies to avoid detection by the immune surveillance, ultimately leading to uncontrolled tumor growth and metastasis. We recently discovered that tumor "weaponizes" a small molecule to kill surrounding T cells. As such, when T cells reach tumor sites, they are rapidly getting killed instead of being able to fight the tumor.

Our preliminary study identified a T cell surface protein receptor for this toxic small molecule, and we also identified intracellular candidate targets that mediate T cell death.

Our main objectives are to first elucidate the molecular mechan...

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T cells are important immune cells that patrol the body and protect us from infection and cancer. Many solid tumors have evolved strategies to avoid detection by the immune surveillance, ultimately leading to uncontrolled tumor growth and metastasis. We recently discovered that tumor "weaponizes" a small molecule to kill surrounding T cells. As such, when T cells reach tumor sites, they are rapid getting killed instead of being able to fight the tumor.

Our preliminary study identified a T cell surface protein receptor for this toxic small molecule, and we also identified intracellular candidate targets that mediate T cell death.

Our main objectives are to first elucidate the molecular mechanism of this new tumor-induced T cell killing pathway, then design therapeutic strategies to selectively block this pathway. We predict that targeting this pathway in T cells will "shield" T cell from tumor killing therefore allowing stronger and longer lasting anti-tumor immunity. Studies proposed here will have tremendous potential in advancing cancer immunotherapy against many hard-to-treat solid tumors.

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