Wee1 identified as a key automotive factor of immune resistance in cancer

Immune control points are regulatory proteins that prevent the immune system from attacking healthy tissues. Some cancer cells use these checkpoints to avoid detection of immunity. Immunological therapy blockage of control points (ICB), which uses antibodies to block these deceptive signals, can free the immune system to destroy cancer.

However, the main challenge in oncology remains: why are some tumors based ICB?

In a breakthrough study, scientists from Korea University discovered a surprising answer: Wee1 protein, traditionally known as a cell cycle regulator and tumor suppressor, can paradoxically drive immunological resistance when they are in the cytoplasm of cancer cells.

Emphasizing the importance of this achievement, Professor Tae Woo Kim from the Faculty of Biochemistry and Molecular Biology at Korea University College of Medicine, Seul, Republic of Korea, reveals, “”. The study was published in volume 13, the issue of 6 magazine on June 4, 2025.

RNA samples were obtained from metastatic patients melanoma and flawless cell lung cancer that underwent ICB treatment. These patients were classified as respondents and not responding, and their transcriptomous signatures were analyzed to understand the levels of WEE1 expression. The team stated that the Wee1 expression was significantly increased in non -aging people, correlating with poor prognosis, high tumor proliferation and cancer parent features (CSC).

The NANOG transcription factor regulates Wee1. Once phosphorylated by the act, Wee1 moves from the nucleus to the cytoplasm, where it activates the HSP90A – TCL1A – Okt loop, maintaining the hyperactivation of the files.

Explaining the molecular mechanism, Dr. Hyo-Jung Lee, the first author of the study, explains “

Importantly, this study reveals the paradoxical role of cytoplasmic Wee1. While its canonical function includes DNA repair and tumor suppression in the nucleus, its non -canonical cytoplasmic role is conducive to the progress of tumor and immune resistance. These discoveries emphasize the potential of the levels of Wee1 expression as predictive biomarkers to choose patients who can use ICB associated therapy.

Discussing the therapeutic implications of WEEI inhibitors, prof. Kim comments,

This evidence study of concepts may also include other cell cycle regulators with similar double functions such as P21, P27 and ChK1, thus expanding the landscape of therapeutic goals and paving the way of developing new treatment strategies.