Objective: We investigated neurotensin receptor 1 (NTSR1) as a potential mediator of the mechanical immune barrier that contributes to T-cell exclusion. Summary Background Data: The efficacy of immunotherapy in advanced colorectal cancer (CRC) is limited by primary resistance, frequently characterized by an “immune-excluded” phenotype where physical and biological barriers prevent effector T-cell infiltration. Through its high-affinity receptor, NTSR1, neurotensin signaling has been implicated i