PD-1/PD-L1 blockade therapy is a promising cancer treatment strategy, which has revolutionized the treatment landscape of malignancies. Over the last decade, PD-1/PD-L1 blockade therapy has been trialed in a broad range of malignancies and achieved clinical success. Despite the potentially cure-like survival benefit, only a minority of patients are estimated to experience a positive response to PD-1/PD-L1 blockade therapy, and the primary or acquired resistance might eventually lead to cancer progression in patients with clinical responses. Accordingly, the resistance to PD-1/PD-L1 blockade remains a significant challenge hindering its further application. To overcome the limitation in therapy resistance, substantial effort has been made to improve or develop novel anti-PD-1/PD-L1 based immunotherapy strategies with better clinical response and reduced immune-mediated toxicity. In this review, we provide an overview on the resistance to PD-1/PD-L1 blockade and briefly introduce the mechanisms underlying therapy resistance. Moreover, we summarize potential predictive factors for the resistance to PD-1/PD-L1 blockade. Furthermore, we give an insight into the possible solutions to improve efficacy and clinical response. In the following research, combined efforts of basic researchers and clinicians are required to address the limitation of therapy resistance.

中文翻译：

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PD-1/PD-L1 阻断癌症免疫疗法的耐药性：机制、预测因素和未来前景。

PD-1/PD-L1阻断疗法是一种很有前途的癌症治疗策略，它彻底改变了恶性肿瘤的治疗格局。在过去的十年中，PD-1/PD-L1阻断疗法已在多种恶性肿瘤中进行了试验并取得了临床成功。尽管具有潜在的类似治愈的生存获益，但据估计，只有少数患者对 PD-1/PD-L1 阻断治疗产生阳性反应，并且原发性或获得性耐药可能最终导致具有临床反应的患者的癌症进展。因此，对 PD-1/PD-L1 阻断的抵抗仍然是阻碍其进一步应用的重大挑战。为了克服治疗耐药性的限制，人们做出了大量努力来改进或开发基于抗PD-1/PD-L1的新型免疫治疗策略，以具有更好的临床反应和降低的免疫介导的毒性。在这篇综述中，我们概述了 PD-1/PD-L1 阻断的耐药性，并简要介绍了治疗耐药的机制。此外，我们总结了 PD-1/PD-L1 阻断耐药的潜在预测因素。此外，我们还深入了解了提高疗效和临床反应的可能解决方案。在接下来的研究中，需要基础研究人员和临床医生的共同努力来解决治疗耐药性的局限性。