肿瘤免疫检查点治疗中的疾病暴发性进展及其应对策略
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摘要
以PD-1/PD-L1等免疫检查点为靶点,应用单克隆抗体加以阻断,从而达到激活免疫系统杀灭肿瘤的目的,是当今肿瘤生物治疗的重要手段。在部分肿瘤患者,免疫检查点抑制剂(ICIs)治疗可完全治愈或者有效抑制肿瘤,显著延长生存期;但是在部分肿瘤患者,ICIs治疗导致病情加重,出现暴发性进展(HPD)的现象,即免疫检查点治疗后肿瘤发生反常的加速生长,首次评效时肿瘤生长速率(TGR)比治疗前增加大于50%(△TGR>50%)。本文重点讨论ICIs治疗中HPD的相关问题,如HPD的发现过程、潜在的病理生理机制,以及未来如何应对这一挑战。
Successful targeting and inhibition of the programmed cell death-1/programmed cell death-ligand 1 immune checkpoint pathways by monoclonal antibody stimulates an immune response against tumors, has led to a rapidly expanding repertoire of immune checkpoint inhibitors(ICIs) for the treatment of various cancers. Immune checkpoint therapy has dramatically changed the therapeutic landscape of certain types of cancers. However, hyperprogressive disease(HPD) is emerging as a new pattern of progression in cancer patients treated with ICIs, characterized as an absolute increase in the tumor growth rate exceeding 50% per month. This article discusses the concept of HPD, hypotheses as to the underlying biology, and what needs to be done to better understand and identify strategies to prevent or overcome HPD related to checkpoint blockade therapy.
Successful targeting and inhibition of the programmed cell death-1/programmed cell death-ligand 1 immune checkpoint pathways by monoclonal antibody stimulates an immune response against tumors, has led to a rapidly expanding repertoire of immune checkpoint inhibitors(ICIs) for the treatment of various cancers. Immune checkpoint therapy has dramatically changed the therapeutic landscape of certain types of cancers. However, hyperprogressive disease(HPD) is emerging as a new pattern of progression in cancer patients treated with ICIs, characterized as an absolute increase in the tumor growth rate exceeding 50% per month. This article discusses the concept of HPD, hypotheses as to the underlying biology, and what needs to be done to better understand and identify strategies to prevent or overcome HPD related to checkpoint blockade therapy.
引文
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