Retrospective Cohort Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 18, 2025; 15(2): 102384
Published online Jun 18, 2025. doi: 10.5500/wjt.v15.i2.102384
Novel association between graft rejection and post-transplant malignancy in solid organ transplantation
Hye Sung Kim, Wongi Woo, Young-Geun Choi, Ankit Bharat, Young Kwang Chae
Hye Sung Kim, Department of Medicine, Temple University Hospital, Philadelphia, PA 19140, United States
Wongi Woo, Department of Medicine, St. Joseph Medical Center, Stockton, CA 95204, United States
Young-Geun Choi, Department of Mathematics Education, Sungkyunkwan University, Seoul 03063, South Korea
Ankit Bharat, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
Young Kwang Chae, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, United States
Co-first authors: Hye Sung Kim and Wongi Woo.
Author contributions: Kim HS and Woo W contributed equally to the following: Conceptualization, data curation, formal analysis, investigation, methodology, software, validation, visualization, original draft preparation, and review and editing of the manuscript; Choi YG contributed to formal analysis, investigation, methodology, visualization, and drafting and reviewing the manuscript; Bharat A contributed to conceptualization, supervision, project administration, and drafting and reviewing the manuscript; Chae YK contributed to conceptualization, supervision, project administration, investigation, methodology, and drafting and reviewing the manuscript. All authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Northwestern Institutional Review Board (IRB ID: STU00207117-MOD0009).
Informed consent statement: Written informed consent for participation was not mandated from participants or their legal guardians/next of kin, in line with national legislation and institutional protocols.
Conflict-of-interest statement: There are no conflicts of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement- checklist of items.
Data sharing statement: sharing statement: Statistical reporting and analysis will be shared by the corresponding author upon reasonable request. To access these reports, please contact ychae@nm.org.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Young Kwang Chae, MD, Professor, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 645 N. Michigan Avenue, Suite 1006, Chicago, IL 60611, United States. chaelabmeeting@gmail.com
Received: October 16, 2024
Revised: December 10, 2024
Accepted: January 9, 2025
Published online: June 18, 2025
Processing time: 127 Days and 13.3 Hours
Abstract
BACKGROUND

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.

AIM

To investigate whether immunosuppression in PTM reduces rejection risk, while immune activation during rejection protects against malignancy.

METHODS

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.

RESULTS

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, P < 0.001], even after excluding mortality cases. Kidney transplant recipients exhibited the most pronounced reduction (HR = 0.22, P < 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, P < 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; P < 0.001) but not in pancreas transplants.

CONCLUSION

RGF reduces PTM risk, particularly in kidney transplants, while PTM decreases RGF risk in kidney, liver, heart, and lung transplants.

Keywords: Graft rejection; Post-transplant malignancy; Transplantation; Transplant immunology; Immunosuppression; Kidney transplant; Liver transplant; Heart transplant; Lung transplant; Pancreas transplant

Core Tip: Our study uncovers a novel inverse relationship between rejection-induced graft failure (RGF) and post-transplant malignancy (PTM) in a cohort of 579905 solid organ transplant recipients. The findings suggest that immune activation during rejection enhances tumor surveillance and lowers malignancy risk, particularly in kidney transplants. In contrast, the immunosuppressive environment associated with PTM reduces the risk of RGF in all organs except the pancreas. These results underscore the need for tailored immunosuppressive strategies that balance the dual risks of rejection and malignancy to improve long-term outcomes in transplant recipients.