Synergistic effect of programmed death-1 inhibitor and programmed death-1 ligand-1 inhibitor combined with chemotherapeutic drugs on DLBCL cell lines in vitro and in vivo

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). Chemotherapy is one of the main treatments for cancer, but the antitumor effect of chemotherapeutic drugs is affected by the patient's immune status. The programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis is an important central checkpoint in tumor progression. The present study demonstrated a significant synergistic effect of PD-1 inhibitor and oxaliplatin, cisplatin, etoposide, cytarabine, ifosfamide and carboplatin. There was no difference in cytotoxicity between the groups with or without PD-L1 inhibitor. It was also observed that cytotoxicity of T cells combined with PD-1 inhibitor against DLBCL cells was inhibited by dexamethasone addition to the culture system at 24, 48 and 72 h. There was no difference in cytotoxicity between the group of dexamethasone added at 96 h and the group without dexamethasone at 96 h. Then, we selected a PD-1 inhibitor combined with a chemotherapeutic regimen in a Pfeiffer cell mouse xenograft model. At 21 days, the reduction in tumor size was more obvious in the DHAP combined with PD-1 inhibitor group (dexamethasone after 96 h of PD-1) compared with that in the DHAP (P=0.007), the PD-1 inhibitor (P=0.001) and the DHAP combined with PD-1 inhibitor (dexamethasone after 24 h of PD-1) (P=0.005) groups. However, the reduction in tumor size was more obvious in the GemOx combined with PD-1 inhibitor group compared with that in the GemOx group (P=0.037). Therefore, the present study demonstrated the synergistic effects of PD-1 inhibitor combined with chemotherapeutic regimens in DLBCL.