The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Immune Checkpoint Inhibitors in Organ Transplant Patients
Abstract
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant. Excluding these patients was deliberate due to concern that immune checkpoint inhibitor therapy could lead to graft rejection. The PD-1 and CTLA-4 pathways are essential to downregulate our immune system in the setting of T-cell activation to prevent autoimmunity. Furthermore, both pathways are implicated in transplanted organ tolerance and modulation of the pathways may inadvertently lead to peripheral transplant rejection. Currently, there are no guidelines for the treatment of patients with immune checkpoint inhibitors in the setting of a prior organ transplant. Thus far, there are only 10 reported cases of patients in the literature who were treated in this setting. Two additional cases are reported herein, including 1 patient with a prior cardiac transplant receiving nivolumab for non–small cell lung cancer. Of the 12 cases, 4 patients experienced organ rejection. From these observations, the authors hypothesize factors that affect safety and of this treatment modality in this patient population. These factors include the integral role of the PD-1 pathway compared with the CTLA-4 pathway in organ acceptance, sequential implementation of different immune checkpoint inhibitor classes, length of time with a transplant before therapy, strength of immunosuppressive agents to prevent organ transplant rejection, and immunogenicity of the particular organ grafted. Although limited cases have been reported, there are circumstances in which immune checkpoint inhibitors have been used in the setting of organ transplantation without resulting in organ rejection. A thorough discussion with the patient of the potential risks, including graft rejection, and benefits of this therapy is necessary before beginning this treatment. More research is needed to explore the safety and efficacy of immune checkpoint inhibitors in the setting of organ transplantation.
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“no data exists on the use of mTORi for secondary prevention14.”
From Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation (2019) · cites this paper as [14]
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Metadata
- Authors
- Kittai, A. S., Oldham, H., Cetnar, J., & Taylor, M.
- Affiliations
- Hematology and Medical Oncology
- Oregon Health & Science University (US)
- Corresponding author
- Kittai, Adam S.
- Cetnar, Jeremy
- Taylor, Matthew
- Venue
- Journal of Immunotherapy
- Published
- 2017-09
- Volume
- 40
- Issue
- 7
- Pages
- 277-281
- ISSN
- 1524-9557 (ISSN-L)
- OpenAlex
- W2737651375
- Cited by
- 151
- References
- 29
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 13 · 2023: 11 · 2022: 21 · 2021: 16 · 2020: 26 · 2019: 29 · 2018: 18 · 2017: 4
- FWCI
- 9.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Immunotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Keywords
- immune checkpoint inhibitors, organ transplantation, graft rejection, PD-1 pathway, nivolumab, non-small cell lung cancer, heart transplantation, immunosuppression, cancer immunotherapy safety
- MeSH terms
- Antineoplastic Agents, Immunological, Aged, Animals, Antineoplastic Combined Chemotherapy Protocols, Combined Modality Therapy, Female, Humans, Immunosuppressive Agents, T-Lymphocyte Subsets, Organ Transplantation, Neoplasms, Second Primary, Treatment Outcome, Disease Progression, Immunomodulation, B7-H1 Antigen, CTLA-4 Antigen, Programmed Cell Death 1 Receptor, Transplant Recipients
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