肿瘤细胞治疗研究
英文原题：Beyond monotherapy: multimodal strategies integrating immune checkpoint inhibitors in lymphoma management.
Beyond monotherapy: multimodal strategies integrating immune checkpoint inhibitors in lymphoma management.
免疫检查点抑制剂（ICIs）的出现彻底改变了淋巴瘤的治疗格局，但其在霍奇金淋巴瘤（HL）和非霍奇金淋巴瘤（NHL）中的疗效差异显著。
免疫检查点抑制剂（ICIs）的出现彻底改变了淋巴瘤治疗格局，尽管其在霍奇金淋巴瘤（HL）与非霍奇金淋巴瘤（NHL）中的疗效差异显著。靶向程序性细胞死亡蛋白1/程序性死亡配体1（PD-1/PD-L1）通路的ICIs在HL中显示出显著疗效，但在包括弥漫大B细胞淋巴瘤在内的NHL亚型中获益有限；在T细胞淋巴瘤和自然杀伤（NK）细胞淋巴瘤中，PD-1抑制剂在结外NK/T细胞淋巴瘤中表现出显著疗效，但大多数外周T细胞淋巴瘤亚型的缓解率仍有限。PD-1/PD-L1轴是淋巴瘤免疫治疗的核心：PD-1/PD-L1阻断可对抗肿瘤免疫逃逸，而CTLA-4抑制则增强淋巴组织中T细胞的早期活化。其他检查点也通过介导T细胞耗竭促进疾病进展，凸显其治疗相关性。本综述阐述了将ICIs与常规疗法（化疗、放疗）、靶向药物及新兴治疗模式联合使用的机制依据和临床意义。协同组合在克服耐药和增强抗肿瘤免疫方面显示出潜力。临床试验强调，PD-1抑制剂联合化疗/放疗方案在特定淋巴瘤中可提高缓解率和生存率。免疫联合疗法在特定亚型中实现更优疗效，尽管免疫相关不良事件增加。通过综合不同联合策略的证据，本观点为临床医生提供了一个超越传统疾病亚型界限的整合框架，为淋巴瘤免疫治疗中的治疗决策提供更广泛的见解。当前挑战包括开发预测性生物标志物和优化免疫相关不良事件的管理。总体而言，将ICIs与互补治疗方式相结合具有变革性潜力，但需要严格的机制探索和临床验证，以最大化治疗指数和缓解的持久性。
The advent of immune checkpoint inhibitors (ICIs) has revolutionized lymphoma therapy, though efficacy varies markedly between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). ICIs targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway show significant efficacy in HL, but limited benefit in NHL subtypes including diffuse large B-cell lymphoma; in T-cell lymphomas and natural killer (NK) cell lymphomas, PD-1 inhibitors demonstrate significant efficacy in extranodal NK/T-cell lymphoma, but response rates remain limited for most peripheral T-cell lymphoma subtypes. The PD-1/PD-L1 axis is central to lymphoma immunotherapy: PD-1/PD-L1 blockade counters tumor immune evasion, whereas CTLA-4 inhibition enhances early T-cell activation in lymphoid tissues. Additional checkpoints also contribute to disease progression by mediating T-cell exhaustion, underscoring their therapeutic relevance. This review delineates the mechanistic rationale and clinical implications of combining ICIs with conventional therapies (chemotherapy, radiotherapy), targeted agents, and emerging modalities. Synergistic combinations have shown promise in overcoming resistance and amplifying antitumor immunity. Clinical trials highlight PD-1 inhibitor-chemotherapy/radiotherapy regimens improving response and survival rates in select lymphomas. Immuno-combination therapies achieve superior efficacy in specific subtypes despite heightened immune-related adverse events. By synthesizing evidence across different combination approaches, this perspective provides clinicians with an integrative framework that transcends traditional disease subtype boundaries, offering broader insights for therapeutic decision-making in lymphoma immunotherapy. Current challenges include developing predictive biomarkers and optimizing management of immune-related adverse events. Collectively, integrating ICIs with complementary modalities offers transformative potential, yet requires rigorous mechanistic exploration and clinical validation to maximize therapeutic index and durability of responses.
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