Unleashing T cell surveillance for the eradication of quiescent persister tumor cells resistant to neoadjuvant chemotherapy - PubMed
4 hours ago
- #CD96
- #persister tumor cells
- #colorectal cancer
- Neoadjuvant chemotherapy (NAC) reduces tumor burden in colorectal cancer (CRC) but has limited impact on long-term patient outcomes.
- Quiescent persister tumor cells (PTCs) are identified as a key factor in treatment failure and correlate with poor long-term prognosis.
- PTCs have aggressive stem-like traits and create an immunosuppressive microenvironment, marked by CD96+CD8+ T cell infiltration in mouse models.
- Depletion of CD96 shifts CD8+ T cells away from exhaustion and promotes memory-like phenotypes through improved mitochondrial function.
- Anti-CD96 therapy effectively eliminates PTCs in preclinical models.
- Engineered EpCAM-targeted CAR-T cells lacking CD96 expression robustly target PTCs and show strong therapeutic potential against CRC.
- CD96 is uncovered as a new vulnerability axis in the PTC-driven microenvironment, offering a promising approach to enhance CRC treatment.