Immune checkpoint inhibitors are used in HCC treatment, but overall response rates for single-agent PD-1/PD-L1 blockers have remained stubbornly low. Using a mouse model of NASH-driven HCC, we show that cotreatment with the safe and inexpensive angiotensin II receptor inhibitor losartan substantially enhanced anti-PD-1-triggered HCC regression. Although losartan did not potentiate the reinvigoration of exhausted CD8+ T cells, it considerably enhanced their intratumoral invasion, which we postulated to be compromised by peritumoral fibrosis. Indeed, the beneficial effect of losartan correlated with inhibition of TGF-β signaling and collagen deposition, and depletion of immunosuppressive fibroblasts. Losartan should be evaluated for its adjuvant activity in HCC patients undergoing PD-1/PD-L1 blocking therapy.
展开▼
