Expression of the High Affinity Neurotensin Receptor Defines an Immune-cold, Poor-prognosis Colorectal Cancer Subtype.
Blocking a specific receptor on colorectal cancer cells may help immune cells infiltrate tumors, potentially enhancing checkpoint immunotherapy effectiveness.
Using TCGA data, Random Forest ML, and independent surgical validation, this study establishes high NTSR1 expression as a driver of immune exclusion and poor prognosis in colorectal cancer through PLXNB3/FLNC/AHNAK2-mediated tumor microenvironment remodeling. Pharmacological NTSR1 blockade with SR48692 reverses T-cell exclusion in 3D models, providing preclinical rationale for combining NTSR1 antagonism with checkpoint immunotherapy to convert immune-cold CRC to immune-responsive tumors.
What the study was
- Study design
- Dual-cohort retrospective analysis (TCGA discovery + University of Kentucky validation) with 3D in vitro tumor spheroid model; Random Forest machine learning classification
- Population
- Colorectal cancer patients (TCGA discovery cohort + University of Kentucky surgical validation cohort)
- Category
- Treatment Innovation
- Maturity
- Exploratory
- Journal
- Annals of Surgery
Why it surfaced
Novel actionable target (NTSR1) for the major unmet need of immunotherapy resistance in MSS/immune-cold CRC, validated across two clinical cohorts with functional in vitro reversal; Annals of Surgery publication adds credibility.
A plain-language summary of published research — not medical advice. Talk to a clinician about your own care.