Highlight
– High-affinity neurotensin receptor 1 (NTSR1) expression identifies a colorectal cancer (CRC) subtype characterized by immune exclusion and poor prognosis.
– NTS/NTSR1 signaling upregulates mechanostructural proteins (PLXNB3, FLNC, AHNAK2) and represses epithelial differentiation transcription factors (CDX2, SATB2), remodeling the tumor microenvironment.
– NTSR1 activation physically restricts T-cell infiltration in 3D tumor models, a phenomenon reversed by NTSR1 antagonist SR48692.
– Targeting the NTS/NTSR1 axis offers a promising strategy to overcome immune exclusion and enhance immunotherapy efficacy in CRC.
