At the Bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy

作者：Intlekofer Andrew M; Thompson Craig B^*

来源：Journal of Leukocyte Biology, 2013, 94(1): 25-39.

DOI：10.1189/jlb.1212621

• tumor
• receptor
• inhibitory
• coinhibitory
• costimulatory
• costimulation
• PD-L1
• ipilimumab

Tumors can avoid immune surveillance by stimulating immune inhibitory receptors that function to turn off established immune responses. By blocking the ability of tumors to stimulate inhibitory receptors on T cells, sustained, anti-tumor immune responses can be generated in animals. Thus, therapeutic blockade of immune inhibitory checkpoints provides a potential method to boost anti-tumor immunity. The CTLA-4 and PD-1Rs represent two T cell-inhibitory receptors with independent mechanisms of action. Preclinical investigations revealed that CTLA-4 enforces an activation threshold and attenuates proliferation of tumor-specific T lymphocytes. In contrast, PD-1 functions primarily as a stop signal that limits T cell effector function within a tumor. The unique mechanisms and sites of action of CTLA-4 and PD-1 suggest that although blockade of either has the potential to promote anti-tumor immune responses, combined blockade of both might offer even more potent anti-tumor activity. See related review At the Bedside: CTLA-4 and PD-1 blocking antibodies in cancer immunotherapy.

• 出版日期2013-7