Non-Hodgkin lymphomas comprise a heterogenous group of disorders which differ in biology. Although response rates are high in some groups, relapsed disease can be difficult to treat, and newer approaches are needed for this patient population. It is increasingly apparent that the immune system plays a significant role in the propagation and survival of malignant cells. Immune checkpoint blocking agents augment cytotoxic activity of the adaptive and innate immune systems and enhance tumor cell killing. Anti-PD-1 and anti-CTLA-4 antibodies have been tested as both single agents and combination therapy. Although success rates with anti-PD-1 antibodies are high in patients with Hodgkin lymphoma, the results are yet to be replicated in those with non-Hodgkin lymphomas. Some lymphoma histologies, such as primary mediastinal B cell lymphoma (PMBL), central nervous system, and testicular lymphomas and gray zone lymphoma, respond favorably to PD-1 blockade, but the response rates in most lymphoma subtypes are low. Other agents including those targeting the adaptive immune system such as TIM-3, TIGIT, and BTLA and innate immune system such as CD47 and KIR are therefore in trials to test alternative ways to activate the immune system. Patient selection based on tumor biology is likely to be a determining factor in treatment response in patients, and further research exploring optimal patient populations, newer targets, and combination therapy as well as identifying biomarkers is needed.

中文翻译：

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使用免疫检查点抑制剂激活非霍奇金淋巴瘤的抗肿瘤免疫反应

非霍奇金淋巴瘤包括一组在生物学上不同的异质性疾病。尽管某些群体的反应率很高，但复发的疾病可能难以治疗，因此需要针对该患者群体采用新的方法。越来越明显的是，免疫系统在恶性细胞的繁殖和存活中起着重要作用。免疫检查点阻断剂增强适应性和先天免疫系统的细胞毒活性并增强肿瘤细胞杀伤。抗 PD-1 和抗 CTLA-4 抗体已作为单一药物和联合疗法进行了测试。尽管抗 PD-1 抗体在霍奇金淋巴瘤患者中的成功率很高，但结果尚未在非霍奇金淋巴瘤患者中复制。一些淋巴瘤组织学，如原发性纵隔 B 细胞淋巴瘤 (PMBL)，中枢神经系统、睾丸淋巴瘤和灰区淋巴瘤对 PD-1 阻断反应良好，但大多数淋巴瘤亚型的反应率较低。因此，其他药物，包括针对适应性免疫系统的药物，如 TIM-3、TIGIT 和 BTLA，以及先天免疫系统，如 CD47 和 KIR，都在试验中，以测试激活免疫系统的替代方法。基于肿瘤生物学的患者选择可能是患者治疗反应的决定性因素，需要进一步研究探索最佳患者人群、新靶点和联合治疗以及识别生物标志物。因此，其他药物，包括针对适应性免疫系统的药物，如 TIM-3、TIGIT 和 BTLA，以及先天免疫系统，如 CD47 和 KIR，都在试验中，以测试激活免疫系统的替代方法。基于肿瘤生物学的患者选择可能是患者治疗反应的决定性因素，需要进一步研究探索最佳患者人群、新靶点和联合治疗以及识别生物标志物。因此，其他药物，包括针对适应性免疫系统的药物，如 TIM-3、TIGIT 和 BTLA，以及先天免疫系统，如 CD47 和 KIR，都在试验中，以测试激活免疫系统的替代方法。基于肿瘤生物学的患者选择可能是患者治疗反应的决定性因素，需要进一步研究探索最佳患者人群、新靶点和联合治疗以及识别生物标志物。