Immune checkpoint receptors in cancer: redundant by design?

Co-inhibitory receptors expressed on activated immune cells function to regulate T cell tolerance to self-antigens, also serving by tumor cells to escape from eradication by the host immune system. Therefore, blockade of immune checkpoint receptors (ICR) has become a promising immunotherapeutic strategy for treatment of a wide variety of cancers. However, blockade of one of the immune checkpoint receptors alone is often not sufficiently effective; co-blockade shows synergic effects in reversing immunosuppression. In this article, we summarize the expression patterns, mechanisms of action of different ICRs as well as the stages and sites they function in, and discuss how they execute non-redundant suppressive effects in anti-tumor immunity.

激活的免疫细胞上表达的共抑制受体具有调节T细胞对自身抗原耐受性的作用，同时也被肿瘤细胞利用以逃避宿主免疫系统的清除。因此，阻断免疫检查点受体（ICR）已成为治疗多种癌症的一种有前景的免疫治疗策略。然而，单独阻断一种免疫检查点受体往往效果不够显著；联合阻断在逆转免疫抑制方面具有协同效应。在本文中，我们总结了不同免疫检查点受体的表达模式、作用机制以及它们发挥作用的阶段和部位，并讨论了它们在抗肿瘤免疫中如何产生非冗余的抑制作用。