A study has shown that the combination of PY314 and pembrolizumab has a favorable safety profile in patients with checkpoint inhibitor (CPI)-refractory metastatic renal cell carcinoma (RCC), but the observed anti-tumor effects were limited, suggesting that targeting TREM2 in combination with PD-1 blockade may not overcome resistance to prior CPI therapy (154). The gene discussed is TREM2; the disease is renal cell carcinoma.