Kim Hye Sung, Woo Wongi, Choi Young-Geun, Bharat Ankit, Chae Young Kwang
Department of Medicine, Temple University Hospital, Philadelphia, PA 19140, United States.
Department of Medicine, St. Joseph Medical Center, Stockton, CA 95204, United States.
World J Transplant. 2025 Jun 18;15(2):102384. doi: 10.5500/wjt.v15.i2.102384.
Advancements in immunosuppressive therapies have improved graft survival by enhancing graft tolerance and preventing organ rejection. However, the risk of malignancy associated with prolonged immunosuppression remains a concern, as it can adversely affect recipients' quality of life and survival. While the link between immunosuppression and increased cancer risk is well-documented, the specific interactions between graft rejection and post-transplant malignancy (PTM) remain poorly understood. Addressing this knowledge gap is crucial for devising immunosuppressive strategies that balance rejection prevention with cancer risk reduction.
To investigate whether immunosuppression in PTM reduces rejection risk, while immune activation during rejection protects against malignancy.
We analyzed data from the United Network for Organ Sharing's Organ Procurement and Transplantation Network database (1987-2023) on adult, first-time, single-organ transplant recipients with no prior history of malignancy (in donors or recipients). Landmark analyses at 1, 2, 3, 5, 10, 15, and 20 years post-transplant, Kaplan-Meier analyses, and time-dependent Cox proportional hazards regression models, each incorporating the temporal dimension of outcomes, assessed the association between rejection-induced graft failure (RGF) and PTM. Multivariate models were adjusted for clinical and immunological factors, including immunosuppression regimens.
The cohort included 579905 recipients (kidney: 386878; liver: 108390; heart: 45046; lung: 37643; pancreas: 1948) with a mean follow-up of 7.3 years and a median age of 50.6 ± 13.2 years. RGF was associated with a reduction in PTM risk across all time points [hazard ratio (HR) = 0.07-0.20, < 0.001], even after excluding mortality cases. Kidney transplant recipients exhibited the most pronounced reduction (HR = 0.22, < 0.001). Conversely, among recipients with PTM, RGF risk decreased across all time points up to 15 years after excluding mortality cases (HR = 0.49-0.80, < 0.001). This risk reduction was observed in kidney, liver, heart, and lung transplants (HRs = 0.90, 0.21, 0.21, and 0.18, respectively; < 0.001) but not in pancreas transplants.
RGF reduces PTM risk, particularly in kidney transplants, while PTM decreases RGF risk in kidney, liver, heart, and lung transplants.
免疫抑制疗法的进步通过增强移植物耐受性和预防器官排斥反应提高了移植物存活率。然而，长期免疫抑制相关的恶性肿瘤风险仍然令人担忧，因为它会对受者的生活质量和存活率产生不利影响。虽然免疫抑制与癌症风险增加之间的联系已有充分记录，但移植物排斥反应与移植后恶性肿瘤（PTM）之间的具体相互作用仍知之甚少。填补这一知识空白对于制定平衡预防排斥反应与降低癌症风险的免疫抑制策略至关重要。
研究PTM中的免疫抑制是否降低排斥反应风险，而排斥反应期间的免疫激活是否预防恶性肿瘤。
我们分析了器官共享联合网络的器官获取与移植网络数据库（1987 - 2023年）中成年首次单器官移植受者的数据，这些受者在供者或受者中均无恶性肿瘤病史。在移植后1、2、3、5、10、15和20年进行标志性分析、Kaplan - Meier分析以及纳入结局时间维度的时间依赖性Cox比例风险回归模型，评估排斥反应诱导的移植物衰竭（RGF）与PTM之间的关联。多变量模型针对临床和免疫因素进行了调整，包括免疫抑制方案。
该队列包括579905名受者（肾脏：386878例；肝脏：108390例；心脏：45046例；肺：37643例；胰腺：1948例），平均随访7.3年，中位年龄为50.6±13.2岁。在所有时间点，RGF均与PTM风险降低相关[风险比（HR）=0.07 - 0.2, <0.001]，即使排除死亡病例后也是如此。肾移植受者的风险降低最为显著（HR = 0.22, <0.001）。相反，在患有PTM的受者中，排除死亡病例后，直至移植后15年的所有时间点，RGF风险均降低（HR = 0.49 - 0.8, <0.001）。这种风险降低在肾、肝、心和肺移植中均有观察到（HR分别为0.9、0.21、0.21和0.18； <0.001），但在胰腺移植中未观察到。
RGF降低PTM风险，尤其是在肾移植中，而PTM降低肾、肝、心和肺移植中的RGF风险。
