Purpose of review: Immunotherapy has shown an unprecedented response in treatment of tumors. However, challenges such as lack of cytotoxic lymphocytes to mount an immune response or development of resistance to therapy can limit efficacy. Here, we discuss alternative checkpoints that can be targeted to improve cytotoxic lymphocyte function while harnessing other components of the immune system.
Recent findings: Blockade of alternative checkpoints has improved anti-tumor immunity in mouse models and is being tested clinically with encouraging findings. In addition to modulating T cell function directly, alternative checkpoints can also regulate activity of myeloid cells and regulatory T cells to affect anti-tumor response. Combination of immune checkpoint inhibitors can improve treatment of tumors by activating multiple arms of the immune system.
Keywords: Alternative checkpoints; Antigen presentation; Checkpoint blockade; Immunosuppression; Immunotherapy; T cell exhaustion.