Tumor Regression and Allograft Rejection after Administration of Anti–PD-1

Lipson, Evan J.; Bagnasco, Serena M.; Moore, Jack; Jang, Sekwon; Patel, Manisha J.; Zachary, Andrea A.; Pardoll, Drew M.; Taube, Janis M.; Drake, Charles G.

doi:10.1056/nejmc1509268

Cited by 247 publications

(180 citation statements)

References 4 publications

(4 reference statements)

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“…These checkpoints might have a role in the rarity of TCMR in biopsies obtained 10 years posttransplantation 46 , which is reminiscent of the phenomenon of Tcell exhaustion 72,73 . A 2016 description of a patient who after 28 years with a sta ble kidney transplant developed uncontrollable TCMR after receiving antiPD1 antibodies to control a cancer, highlights the potential role of these checkpoints in preventing late TCMR 74 .…”

Section: Molecular Landscapes Of Rejectionmentioning

confidence: 99%

Molecular assessment of disease states in kidney transplant biopsy samples

2016

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Progress in renal transplantation requires improved understanding and assessment of rejection and injury. Study of the relationship between gene expression and clinical phenotypes in kidney transplant biopsy samples has led to the development of a system that enables diagnoses of specific disease states on the basis of messenger RNA levels in the biopsy sample. Using this system we have defined the molecular landscape of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), acute kidney injury (AKI), and tubular atrophy and interstitial fibrosis. TCMR and ABMR share IFNγ-mediated effects and TCMR has emerged as a cognate T cell-antigen presenting cell process in the interstitium, whereas ABMR is a natural-killer-cell-mediated process that occurs in the microcirculation. The specific features of these different processes have led to the creation of classifiers to test for TCMR and ABMR, and revealed that ABMR is the principal cause of kidney transplant deterioration. The molecular changes associated with renal injury are often more extensive than suggested by histology and indicate that the progression to graft failure is caused by continuing nephron injury, rather than fibrogenesis. In summary, advances in the molecular assessment of disease states in biopsy samples has improved understanding of specific processes involved in kidney graft outcomes.

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Section: Molecular Landscapes Of Rejectionmentioning

confidence: 99%

Molecular assessment of disease states in kidney transplant biopsy samples

2016

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“…Four patients (2 liver and 2 kidney recipients) received anti-CLTA-4, with all 4 showing tumor regression without long-term impairment of graft function 216-218 . One kidney transplant recipient showed tumor regression with anti-PD-1 therapy, but lost kidney graft to acute cellular rejection 219 . One kidney transplant recipient received initial anti-CTLA-4 therapy without rejection or tumor regression, but follow-up anti-PD-1 therapy precipitated graft rejection while inducing tumor shrinkage 220 .…”

Section: Anti-cd28 Antibodiesmentioning

confidence: 99%

Impact of Immune-Modulatory Drugs on Regulatory T Cell

2016

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Immunosuppression strategies that selectively inhibit effector T cells while preserving and even enhancing CD4+FOXP3+ regulatory T cells (Treg) permit immune self-regulation and may allow minimization of immunosuppression and associated toxicities. Many immunosuppressive drugs were developed before the identity and function of Treg were appreciated. A good understanding of the interactions between Treg and immunosuppressive agents will be valuable to the effective design of more tolerable immunosuppression regimens. This review will discuss preclinical and clinical evidence regarding the influence of current and emerging immunosuppressive drugs on Treg homeostasis, stability, and function as a guideline for the selection and development of Treg-friendly immunosuppressive regimens.

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“…Although Lipson et al [51] had initially reported the successful administration of ipilimumab to 2 kidney transplantation patients with metastatic melanoma without any signs of rejection, they recently reported a case of tumor regression but allograft rejection after administration of pembrolizumab [52]. In addition, 3 cases of rejection were reported with the use of nivolumab in kidney transplant patients with melanoma [53,54,55].…”

Section: Introductionmentioning

confidence: 99%

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

Wanchoo

Karam²,

Uppal³

et al. 2017

Am J Nephrol

11,131

256

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Background: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. Summary: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.

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Tumor Regression and Allograft Rejection after Administration of Anti–PD-1

Cited by 247 publications

References 4 publications

Molecular assessment of disease states in kidney transplant biopsy samples

Molecular assessment of disease states in kidney transplant biopsy samples

Impact of Immune-Modulatory Drugs on Regulatory T Cell

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

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