Drug resistance of tumor cells to chemotherapy is limiting the therapeutic efficacy of most anticancer drugs and represents a major obstacle in medical oncology. However, treatment of various human malignancies with biologics, mostly monoclonal antibodies (mAbs), is not limited by such chemoresistance mechanisms. However, other resistance or evasion mechanisms limit the efficacy to anticancer therapeutic mAbs that engage tumor-associated antigens on the surface of the malignant cells. Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology. These mAbs do not directly attack the malignant cells as most anticancer mAbs; rather, they enhance the anti-tumor response of the immune system by targeting immune regulatory pathways. Three mAbs targeting immune checkpoint molecules are currently used in the clinic and new mAbs that target other potential inhibitory targets are being actively investigated. This therapeutic approach, while proving as highly beneficial for many patients, is prone to toxicities and side effects of an autoimmune nature. Defining suitable management algorithms and biomarkers that predict therapeutic effects and adverse toxicity are required to provide survival benefit for larger numbers of cancer patients. Overcoming these challenges, along with opportunities for new agents and combinatorial strategies are the main focus of immune checkpoint blockade research today.

肿瘤细胞对化学疗法的耐药性限制了大多数抗癌药物的治疗效果，并代表了医学肿瘤学的主要障碍。但是，用这种化学药物（主要是单克隆抗体（mAb））对各种人类恶性肿瘤的治疗不受这种化学耐药机制的限制。但是，其他抗性或逃逸机制将其功效限制在与恶性细胞表面上与肿瘤相关的抗原结合的抗癌治疗性单克隆抗体上。免疫检查点封闭性单克隆抗体被认为是临床肿瘤学中一种有前途的治疗方法。这些mAb不会像大多数抗癌mAb一样直接攻击恶性细胞。相反，它们通过靶向免疫调节途径来增强免疫系统的抗肿瘤反应。目前在临床中使用了三种靶向免疫检查点分子的mAb，并且正在积极研究靶向其他潜在抑制靶标的新型mAb。尽管该治疗方法对许多患者证明是高度有益的，但它易于产生自身免疫性质的毒性和副作用。需要定义合适的管理算法和生物标记物以预测治疗效果和不良毒性，才能为更多的癌症患者提供生存益处。克服这些挑战，以及获得新药和组合策略的机会，是当今免疫检查点封锁研究的主要重点。虽然被证明对许多患者非常有益，但容易产生自身免疫性质的毒性和副作用。需要定义合适的管理算法和生物标记物以预测治疗效果和不良毒性，才能为更多的癌症患者提供生存益处。克服这些挑战，以及获得新药和组合策略的机会，是当今免疫检查点封锁研究的主要重点。虽然被证明对许多患者非常有益，但容易产生自身免疫性质的毒性和副作用。需要定义合适的管理算法和生物标记物以预测治疗效果和不良毒性，才能为更多的癌症患者提供生存益处。克服这些挑战，以及获得新药和组合策略的机会，是当今免疫检查点封锁研究的主要重点。