本研究旨在评价特瑞普利单抗联合治疗的有效性、安全性及免疫功能，旨在为特瑞普利单抗的临床联合使用以及后续癌症治疗适应症的开发提供参考。该Meta分析通过检索PubMed、 Cochrane Library、Web of Science、EMBASE、CNKI 数据库和万方数据库截止至 2023 年 9 月 22 日。仅选择了接受特瑞普利单抗联合治疗的癌症参与者（包括联合组和对照组）的随机对照试验 (RCT)。完全缓解率（CR）、客观缓解率（ORR）、总生存期（OS）、无进展生存期（PFS）、治疗相关不良反应（AE）和免疫相关不良反应（irAE）以及免疫学临床结果提取并评估功能指数（CD3、CD4、CD8和CD4/CD8 T细胞比率）。选择适当的随机或固定效应模型来使用 Stata 软件（版本 12.0）计算汇总效应估计。进行亚组分析以评估 PD-L1 表达是否对 PFS 产生影响。采用 Egger 检验衡量发表偏倚。共有 11 项随机对照试验，涉及 1856 名患者，符合纳入标准。特瑞普利单抗联合化疗和特瑞普利单抗联合靶向治疗均具有更好的 CR [RR = 1.74, 95% CI (1.23, 2.45), P = 0.002]、OS [HR = 1.94, 95% CI (1.76, 2.15), P < 0.001] 和 PFS [HR = 1.70, 95% CI (1.57, 1.83), P < 0.001]，并且 ORR 有所改善 [RR = 1.21, 95% CI (1.09, 1.35), P = 0.001]与单一疗法相比，特瑞普利单抗加化疗而不是加靶向治疗。亚组分析显示，无论 PD-L1 阳性还是阴性，特瑞普利单抗联合化疗均可延长 PFS [HR = 1.78，95% CI (1.60，1.98)，P < 0.001； HR = 1.60，95% CI (1.37，1.87)，P < 0.001]。此外，特瑞普利单抗联合方案显着增加了 CD3、CD4 和 CD4 /CD8 T 细胞的比例 [SMD = 0.79，95% CI (0.19，1.40)，p = 0.01； SMD = 1.40，95% CI (0.72，2.07)，p < 0.001； SMD = 1.46，95% CI (0.64，2.28)，p < 0.001]。任何级别 [RR = 1.65, 95% CI (1.25, 2.18), P < 0.001] 和 3 级或更严重的 irAE [RR = 1.65, 95% CI (1.25, 2.18), P < 0.001] 的发生率均较高特瑞普利单抗联合治疗方案与单一治疗方案相比，但治疗相关 AE 没有发现差异。敏感性分析表明，没有个别研究对汇总结果产生影响。根据现有数据，特瑞普利单抗联合化疗和特瑞普利单抗联合靶向治疗均表现出优异的临床结果和细胞免疫调节作用，但代价是更大但可控制的毒性。需要进行更多的临床试验，以进一步评估其他特瑞普利单抗联合治疗方案的有效性和安全性。版权所有 © 2023 Elsevier B.V. 保留所有权利。

This study was performed to evaluate the efficacy, safety and immunological function of toripalimab combination therapy, aiming to provide a reference for the clinical combined use of toripalimab and the development of subsequent indications for cancer treatment.The meta-analysis was conducted by searching PubMed, Cochrane Library, Web of Science, EMBASE, CNKI database and Wanfang database until September 22, 2023. Only randomized controlled trials (RCTs) that involved cancer participants that received toripalimab combination therapy including a combination and control group were selected. The clinical outcomes of complete response rate (CR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), treatment related adverse effects (AEs) and immune-related adverse effects (irAEs) and immunological function index (CD3+, CD4+, CD8+ and CD4+/CD8+ T cells ratio) were extracted and evaluated. A random or fixed-effects models, as appropriate, were selected to calculate pooled effect estimates using Stata software (version 12.0). Subgroup analysis was done to estimate whether the effects of PD-L1 expression on PFS. Egger's test were carried out to measure publication bias.A total of 11 RCTs involving 1856 patients met the inclusion criteria. Both toripalimab plus chemotherapy and toripalimab plus targeted therapy had a trend of better CR [RR = 1.74, 95%CI (1.23, 2.45), P = 0.002], OS [HR = 1.94, 95%CI (1.76, 2.15), P < 0.001] and PFS [HR = 1.70, 95%CI (1.57, 1.83), P < 0.001], and an improvement of ORR [RR = 1.21, 95%CI (1.09, 1.35), P = 0.001] was found with toripalimab plus chemotherapy while not that plus targeted therapy compared to monotherapy. Subgroup analysis showed that toripalimab plus chemotherapy extended PFS whether PD-L1 positive or negative [HR = 1.78, 95%CI (1.60, 1.98), P < 0.001; HR = 1.60, 95%CI (1.37, 1.87), P < 0.001]. Additionally, toripalimab combined regimens significantly increased the proportion of CD3+, CD4+, and CD4+/CD8+ T cells [SMD = 0.79, 95% CI (0.19, 1.40), p = 0.01; SMD = 1.40, 95% CI (0.72, 2.07), p < 0.001; SMD  = 1.46, 95% CI (0.64, 2.28), p < 0.001]. The incidence of any grade [RR = 1.65, 95%CI (1.25, 2.18), P < 0.001] and grade 3 or worse irAEs [RR = 1.65, 95%CI (1.25, 2.18), P < 0.001] were higher with toripalimab combined regimens as compared to single treatment while no difference was found for treatment related AEs. Sensitivity analysis indicated that no individual study had influence on the pooled results.Based on the available data, both toripalimab plus chemotherapy and toripalimab plus targeted therapy demonstrated superior clinical outcomes and regulation of cellular immunity at the cost of greater but manageable toxicity. More clinical trials need to be performed to further evaluate the efficacy and safety for other toripalimab combined regimens.Copyright © 2023 Elsevier B.V. All rights reserved.