Initially understood for its physiological maintenance of self-tolerance, the immune checkpoint molecule has recently been recognized as a promising anti-cancer target. There has been considerable interest in the biology and the action mechanism of the immune checkpoint therapy, and their incorporation with other therapeutic regimens. Recently the small-molecule inhibitor (SMI) has been identified as an attractive combination partner for immune checkpoint inhibitors (ICIs) and is becoming a novel direction for the field of combination drug design. In this review, we provide a systematic discussion of the biology and function of major immune checkpoint molecules, and their interactions with corresponding targeting agents. With both preclinical studies and clinical trials, we especially highlight the ICI + SMI combination, with its recent advances as well as its application challenges.

最初因其生理上的自我耐受性而被理解，最近，免疫检查点分子被公认为是有前途的抗癌靶标。人们对免疫检查点疗法的生物学和作用机理以及将其与其他治疗方案结合在一起产生了极大的兴趣。最近，小分子抑制剂（SMI）已被确定为免疫检查点抑制剂（ICIs）的有吸引力的组合伙伴，并正在成为组合药物设计领域的新方向。在这篇综述中，我们对主要免疫检查点分子的生物学和功能，以及它们与相应靶向剂的相互作用进行了系统的讨论。通过临床前研究和临床试验，我们特别强调了ICI + SMI组合，