Inventors demonstrated that an epigenetic regulator CBX3 antagonizes IFNγ signalling via directly repressing the transcription of two key interferon-stimulated immune genes, STAT1 and PD-L1. The key role of CBX3 in repressing STAT1 and PD-L1 transcription suggests that CBX3 is an important checkpoint to control immune genes/’ activation in response to different ligands/’ stimulation, such as the important immune modulator IFNγ, which placed CBX3 in a key position to keep colon immune homeostasis.
This role placed also CBX3 in a key position to keep colon immune homeostasis. These studies have started to reveal a new role of CBX3 in controlling the colon epithelium inflammatory response, in addition to its classical role in the formation and stabilization of heterochromatin.
Particularly, low CBX3 expression is associated with better CRC patients/’ overall
survival. Corresponding to this result, CBX3 depletion makes IFNγ-insensitive CRC cells dramatically regain IFNγ sensitivity, which significantly increases CRC cells/’ chemosensitivity under IFNγ stimulation.
Accordingly, the invention relates to a Chromobox protein homolog 3(CBX3) inhibitor for use in the treatment of cancer in a subject in need thereof.