NEK8 kinase-mediated lactate increase impairs antitumor immunity decreasing radiotherapy sensitivity in colorectal cancer - PubMed
5 hours ago
- #Radioresistance
- #Colorectal cancer
- #NEK8 kinase
- NEK8 kinase, highly expressed in colorectal cancer (CRC), promotes radioresistance by suppressing anti-tumor immunity.
- In radiation-resistant tumors, NEK8 phosphorylates LDHA, leading to lactate overproduction, which silences antigen presentation and impairs CD8+ T cell function.
- Pharmacological inhibition of NEK8 with CX6258 restores CD8+ T cell infiltration and enhances local and systemic tumor control after radiotherapy.
- NEK8 is identified as a therapeutic target to overcome radioresistance and induce abscopal responses in CRC.