PD-L1 on lymphatic endothelium inside tumor: a novel predictor for the efficacy of anti-angiogenesis (anlotinib) plus anti-PD-L1 antibody

Abstract Objective To elucidate the predictive power of programmed death receptor ligand (PD-L) 1 on endothelial cells of lymphatic (LECs) on the efficacy of anlotinib plus PD-L1 antibody and screen the advantageous population of treatment. Methods The positive rate of PD-L1 on LECs and tumor cells (TCs) was assessed through pretherapeutic paraffin sections in an Ib clinical trial of TQ-B2450 (PD-L1 antibody) alone or in combination with anlotinib on non-small cell lung cancer (NSCLC). The progression-free survival (PFS) of different PD-L1 expressions was compared. Results In 75 cases, mPFS of the cases receiving TQB2450 with anlotinib(10mg and 12mg) (161 and 190 days) was longer than for those receiving TQB2450 alone (61 days) (HR10mg = 0.390 [95%CI, 0.201–0.756], P = 0.005; HR12mg = 0.397 [95%CI, 0.208–0.756], P = 0.005). Similar results were exhibited among 58 patients with high PD-L1 expression on LECs and TCs (159 days and 209 days vs 82 days, HR10mg = 0.445 [95%CI, 0.210–0.939], P = 0.034; HR12mg = 0.369 [95%CI, 0.174–0.784], P = 0.009;). mPFS between TQ-B2450 or with combined therapy revealed no difference in 13 low/no LEC-expressed PD-L1 and 4 low TC-expressed PD-L1 patients. Conclusion Monoimmunotherapy is unsatisfiedly effective in patients with high PD-L1 expression LECs; anlotinib may increase the efficacy by downregulating PD-L1 expression on lymphatic endothelial cells, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing antiangiogenic therapy.