抗PD-1（程序性死亡1）/B7-H1（B7同源物1）路径的抗体（anti-PD疗法）所带来的改变性成功已经革命性地改变了癌症治疗。然而，只有少数实体肿瘤和一些造血恶性肿瘤的患者对抗PD疗法有反应，而其他患者失败的原因不太清楚。通过分解抵抗其的机制，目前的研究表明，肿瘤微环境是抵抗的主要发生地点。此外，抵抗机制似乎具有高度的异质性。在这里，我们讨论最近的人类癌症数据，以确定抗PD疗法的抵抗机制。我们审查了基于免疫的抵抗机制的证据，例如新抗原的丢失，抗原呈递和干扰素信号缺陷，免疫抑制分子，以及T细胞的排斥。我们还审查了新兴抵抗抗-PD疗法的临床证据，如代谢、微生物群落和表观遗传学的改变。最后，我们讨论克服抗-PD疗法的抵抗策略，并强调需要根据正常癌症免疫治疗的概念开发其他免疫疗法。

The transformative success of antibodies targeting the PD-1 (programmed death 1)/B7-H1 (B7 homolog 1) pathway (anti-PD therapy) has revolutionized cancer treatment. However, only a fraction of patients with solid tumors and some hematopoietic malignancies respond to anti-PD therapy, and the reason for failure in other patients is less known. By dissecting the mechanisms underlying this resistance, current studies reveal that the tumor microenvironment is a major location for resistance to occur. Furthermore, the resistance mechanisms appear to be highly heterogeneous. Here, we discuss recent human cancer data identifying mechanisms of resistance to anti-PD therapy. We review evidence for immune-based resistance mechanisms such as loss of neoantigens, defects in antigen presentation and interferon signaling, immune inhibitory molecules, and exclusion of T cells. We also review the clinical evidence for emerging mechanisms of resistance to anti-PD therapy, such as alterations in metabolism, microbiota, and epigenetics. Finally, we discuss strategies to overcome anti-PD therapy resistance and emphasize the need to develop additional immunotherapies based on the concept of normalization cancer immunotherapy.