Send to

Choose Destination
Front Immunol. 2015 Aug 21;6:418. doi: 10.3389/fimmu.2015.00418. eCollection 2015.

Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators.

Author information

Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH , USA.


In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy.


BTLA; LAG-3; TIGIT; TIM-3; VISTA; autoimmunity; cancer immunotherapy; negative checkpoint regulators

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center