A combination of PD‑1/PD‑L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)

Abstract

Programmed cell death protein‑1 (PD‑1)/programmed death protein ligand‑1 (PD‑L1) inhibitors for treatment of a various types of cancers have revolutionized cancer immunotherapy. However, PD‑1/PD‑L1 inhibitors are associated with a low response rate and are only effective on a small number of patients with cancer. Development of an anti‑PD‑1/PD‑L1 sensitizer for improving response rate and effectiveness of immunotherapy is a challenge. The present study reviews the synergistic effects of PD‑1/PD‑L1 inhibitor with oncolytic virus, tumor vaccine, molecular targeted drugs, immunotherapy, chemotherapy, radiotherapy, intestinal flora and traditional Chinese medicine, to provide information for development of effective combination therapies.

Keywords: oncolytic virus; cancer vaccine; molecular targeted therapy; immunotherapy; intestinal flora; Traditional Chinese Medicine.

Figure 1.

Schematic diagram of combined treatment regimen for PD-1/PD-L1 inhibitors. PD-1, programmed cell death protein-1; PD-L1, programmed death protein ligand-1.

Figure 2.

Schematic diagram of a combination therapy comprising molecular targeting drugs and PD-1/PD-L1 inhibitors. Current and emerging molecular targeting drugs. Various molecular targets expressed on T cells and tumor cells are shown. Immune molecular targets such as PD-1, LAG-3, TIM-3, TIGIT, 4-1BB, CTLA-4, IDO bound to their respective specific antibodies, triggering a positive signal to T cells response. Inhibition of VEGF and EGFR mediated angiogenesis. PD-1, programmed cell death protein-1; PD-L1, programmed death protein ligand-1; LAG3, lymphocyte activation gene-3; TIM-3, T cell immunoglobulin mucin 3; TIGIT, T cell immunoreceptor with Ig and ITIM domains; CTLA-4, cytotoxic T-lymphocyte antigen-4; IDO, indoleamine 2,3-dioxygenase; VEGF, vascular endothelial growth factor; EGFR, epidermal growth factor receptor.