Immunotherapy rechallenge in gastric cancer: resistance mechanisms, molecular stratification, and precision decision-making - PubMed
3 hours ago
- #gastric cancer
- #immune resistance
- #immunotherapy
- Immunotherapy rechallenge in gastric cancer is an investigational strategy for patients who initially benefit from immune checkpoint inhibitors but later progress due to acquired resistance.
- Resistance mechanisms include tumor-intrinsic changes like plasticity and impaired antigen presentation, as well as a suppressive tumor microenvironment and T-cell exhaustion involving compensatory checkpoints such as LAG-3, TIM-3, TIGIT, and VISTA.
- Molecular stratification, particularly in EBV-positive or MSI-H/dMMR tumors, is crucial for decision-making, but there is a need for prospective trials, validated biomarkers, and careful toxicity monitoring to establish rechallenge as a precision therapy approach.