Figure 2.

Schematic of antitumor immune cycle. The immune cycle starts from the production of neoantigens in dying or dead OS cells, endocytosed by APCs for presentation or cross-presentation on MHC. Then, the antigen-loading APCs migrate to the draining lymph nodes to activate antigen-specific T cells. Activated T cells then infiltrate the tumor cells to drive adaptive immune response and to restrain tumor growth. These antitumor immune responses are modified by immune checkpoint mechanisms. The interaction of PD-1 and PD-L1 inhibits intracellular signaling pathways on T cell activation, whereas CTLA-4 prompts inhibitory effects by competitively depriving CD28 ligand and mechanistically binding B7 molecules. Antibodies that affect ICIs may sustainably stimulate the antitumor immune response in patients with OS. OS, osteosarcoma; APCs, antigen-presenting cells; MHC, major histocompatibility complex; PD-1, programmed cell death receptor-1; CTLA-4, cytotoxic T lymphocyte-associated protein 4; B7-H3, B7 homolog 3; PD-L1/PD-L2, programmed cell death receptor-1/2 ligand; ICIs, immune checkpoint inhibitors.