Brief Report: Low Delta-like Ligand 3 expression and T Cell Exhaustion Drive Resistance to Tarlatamab combined with anti-PD-1 in Small-Cell Lung Cancer - PubMed
3 hours ago
- #tumor microenvironment
- #immunotherapy resistance
- #small-cell lung cancer
- The study investigates resistance mechanisms to tarlatamab plus anti-PD-1 therapy in small-cell lung cancer (SCLC).
- Two patients with extensive-stage SCLC were analyzed using multiplexed immunohistochemistry on tumor samples before and after progression.
- Post-resistance tumor cells showed a phenotypic shift with reduced synaptophysin and low DLL3 expression.
- The tumor microenvironment at progression had increased exhausted CD8+ T cells (expressing PD-1, TIGIT, LAG-3) and immunosuppressive cells like CTLA-4 regulatory T cells and M2 macrophages.
- Resistance was linked to low DLL3 expression and an immunosuppressive TME, suggesting combination therapies with checkpoint blockade or myeloid-targeted approaches may improve outcomes.