Post renal-transplant malignancy surveillance

Manickavasagar, Revathy; Thuraisingham, Raj

doi:10.7861/clinmed.2019-0423

Cited by 20 publications

(18 citation statements)

References 23 publications

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“…A better understanding of the development of donor-specific hyporesponsiveness (DSH) in recipient T cells could guide lowering of immunosuppressive medication in the years after transplantation. Less immunosuppression would vastly reduce the risk of infection, cancer and cardiovascular disease, long-term unwanted side effects especially prevalent in elderly kidney transplant recipients (2,3).…”

Section: Introductionmentioning

confidence: 99%

Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation

et al. 2021

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Development of T-cell hyporesponsiveness to donor antigen may explain the substantial decreased risk for acute rejection in the years following kidney transplantation. The underlying mechanisms of donor-specific hyporesponsiveness (DSH) are largely unknown but may allow for lowering of immunosuppressive medication. Due to the onset of DSH being more rapid and pronounced in older recipients (+55 years), we hypothesized that immunosenescence/exhaustion of T lymphocytes would be a contributing factor. This study tested whether donor-reactive recipient T cells become hyporesponsive due to exhaustion from continuous stimulation by donor antigen. Circulating donor-reactive T cells of both young and elderly stable kidney transplant recipients (N=17) before and 3-5 years after transplantation were analyzed at the single cell level for expression of exhaustion markers by multi-parameter flow cytometry followed by unsupervised and unbiased clustering. Clusters containing cells of a particular expression profile with significant differential abundance after transplantation were identified and further analyzed. Unexpectedly, our results do not demonstrate an increase in exhausted donor antigen-reactive T cells post transplantation. Instead, we demonstrate a significant decrease in donor antigen-reactive CD4+ T cells expressing T cell immunoglobulin and ITIM domain (TIGIT) long after transplantation. Further analysis at earlier timepoints indicated that this decrease is already present at six months post transplantation. Characterization of these CD4+ T donor-reactive cells expressing TIGIT revealed them to have a predominantly central and effector memory T cell phenotype and a highly poly-functional cytokine expression profile. This study has therefore identified TIGIT as a marker for a previously undescribed polyfunctional donor-reactive CD4+ T cell population whose decline following kidney transplantation may explain development of DSH.

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Section: Introductionmentioning

confidence: 99%

Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation

et al. 2021

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“…In conclusion, this study reaffirmed a higher risk of malignancy among KT recipients for 14 of 29 cancer types, most of which were diagnosed earlier than the control group. Despite the life-threatening impact of post-transplant malignancies, cancer screening in KT recipients generally follows the guidelines for the general population because of the lack of well-designed randomized controlled trials in this at-risk population [ 39 , 40 ]. Given differential risk patterns in some cancers according to age and sex, our results suggest that focused and more thorough screening for those cancer types may be warranted for a subset of KT recipients.…”

Section: Discussionmentioning

confidence: 99%

Risk of malignancy in kidney transplant recipients: a nationwide population-based cohort study

2022

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Background Post-transplant malignancy is major morbidity complicated in kidney transplantation (KT). In Korea, a few studies have investigated the sex- and age-dependent risk for post-transplant malignancy among KT recipients on a large scale. Methods We utilized a national health insurance database in Korea to investigate the relative risk of post-transplant malignancy in 12,634 KT recipients between 2007 and 2017. The same number of patients with acute appendicitis was included as a control group. The relative risk of malignancy was estimated using a multivariable-adjusted Cox model, and interaction analysis was performed to investigate age- and sex-predominant patterns. Results KT recipients had an overall 1.8-fold higher risk for post-transplant malignancy with an increased risk for 14 of 29 cancer types, among which Kaposi’s sarcoma, non-Hodgkin’s lymphoma, kidney, uterus, and bladder/urinary tract cancers were most prominent. Although the overall risk for post-transplant malignancy was similar between male and female KT recipients, head and neck cancer had a higher risk among male KT recipients, whereas non-Hodgkin’s lymphoma and bladder/urinary tract cancer had a higher risk among female KT recipients. Overall, the young (< 50 years) KT recipients had a higher risk for post-transplant malignancy than older ones (≥ 50 years), whose pattern was most prominent in non-Hodgkin’s lymphoma. In contrast, breast and nonmelanoma skin cancer showed a higher risk among older KT recipients. Conclusion KT recipients had an increased risk for a wide range of cancer types, some of which showed differential risk patterns with age and sex. Our result suggests that focused screening for predominant post-transplant malignancies may be an effective strategy for selected KT recipients.

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“…Some articles report a low incidence rate of PCa, so that an active surveillance program in this population is not recommended. 1 Nevertheless, treatment of PCa in RTRs is a challenging issue that has been discussed by many authors over the years. 4 Prostate irradiation is a therapeutic option that needs to be explored as this subset of patients is often excluded from surgical or medical interventions due to possible toxicities.…”

Section: Introductionmentioning

confidence: 99%

“…Cancer development after KT is an important issue, as a large percentage of these patients are diagnosed with cancer. 1 The immunosuppressive agents employed in renal transplant recipients (RTRs) are held accountable for the rising number of malignancies, which are mainly represented by nonsolid neoplasms such as lymphomas. According to some authors, the number of urologic cancers such as prostate cancer (PCa) after KT has increased 2 ; that could be partly explained by prolonged survival after transplant and the rising age of RTRs.…”

Section: Introductionmentioning

confidence: 99%

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Radiotherapy in prostate cancer after kidney transplant in 6 cases

Detti

Stocchi

Mariotti

et al. 2021

Tumori

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Background: Patients who received a kidney transplant (KT) are described in literature as a group with a higher incidence of malignant neoplasms compared to the general population. Cancer development after KT has become a major issue, as a remarkable percentage of patients are diagnosed with cancer. Treatment of prostate cancer (PCa) in renal transplant recipients (RTRs) is a challenging issue that has been discussed by many authors over the years, but evidence is sparse and often includes conflicting reports. Among the therapeutic options for PCa in these patients, prostate irradiation represents a valuable alternative to surgery or other systemic therapies, as RTRs are often ineligible for these treatments. Objective: To report six cases treated at our institution between 1998 and 2017 and discuss the available literature. Methods: Patients’ characteristics were reported along with biochemical status at diagnosis, type of immunosuppressive treatment, radiation therapy technique, and dose to transplanted kidney. Results: Overall, prostate irradiation was delivered respecting the dose constraints and patients showed good tolerance with no reports of acute or late transplanted kidney injury. Conclusions: Our experience confirms that prostate radiotherapy for RTRs is feasible and effective and represents a valid option that should be considered by the multidisciplinary team.

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Post renal-transplant malignancy surveillance

Cited by 20 publications

References 23 publications

Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation

Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation

Risk of malignancy in kidney transplant recipients: a nationwide population-based cohort study

Radiotherapy in prostate cancer after kidney transplant in 6 cases

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