Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair

  title={Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair},
  author={Christiane Kuschal and Kai M. Thoms and Steffen Schubert and Annika Sch{\"a}fer and Lars Boeckmann and Michael P. Sch{\"o}n and Steffen Emmert},
  journal={Experimental Dermatology},
Abstract:  UV‐induced skin cancers comprise a major problem in organ transplant recipients (OTRs). Cyclosporin A, a calcineurin inhibitor, is used as a standard immunosuppressant and clearly increases the skin cancer risk. Azathioprine does not appear to result in such an increase in skin cancer risk, and mTOR inhibitors are associated with an even lesser skin cancer risk. The underlying molecular mechanisms of these clinically important differences among immunosuppressants are still unclear… 

Skin cancer in organ transplant recipients: more than the immune system.

Cancer and mTOR Inhibitors in Transplant Recipients

There is insufficient evidence for the primary use of mTORis as protective agents against most other cancer types, and recent meta-analyses and randomized trials on secondary prevention of squamous cell carcinoma observed a reduction in cumulative tumor load.

Skin cancer in organ transplant recipients : histopathological and epidemiological studies

Only very few cases demonstrated abundant tumorinfiltrating lymphocytes (TILs), indicating that more variables than just millimeter thickness may be associated with prognosis of posttransplantation melanoma, underscore the importance of regular skin screening in OTRs.

Calcineurin inhibitor (CNI)‐associated skin cancers: New insights on exploring mechanisms by which CNIs downregulate DNA repair machinery

The use of the calcineurin inhibitors (CNI) cyclosporine (CsA) and tacrolimus remains a cornerstone in post‐transplantation immunosuppression, and it is unknown which isoform regulates UV‐induced DNA repair, which is the focus of this review.

Epidemiology of keratinocyte carcinomas after organ transplantation

International variation in KC is described and trends in immunosuppressive regimens, the role of ultraviolet susceptibility and exposure, and the contribution of genetics to tumour development are focused on.

Sirolimus for Secondary Prevention of Skin Cancer in Kidney Transplant Recipients: 5-Year Results.

  • J. DantalE. Morelon S. Euvrard
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2018
In kidney transplant recipients with previous cutaneous squamous cell carcinomas, the antitumoral effect of conversion from calcineurin inhibitors to sirolimus was maintained at 5 years, and siro Limus tolerance was satisfactory.

Reducing skin malignancy risk in organ transplant recipients.

Clinical efforts aimed at reduction in skin cancers in this high-risk population include increased education and surveillance, aggressive treatment of skin cancers and pre-cancers, changes to immunosuppressive regimens, and retinoid chemoprevention.

Update: Solar UV Radiation, Vitamin D, and Skin Cancer Surveillance in Organ Transplant Recipients (OTRs).

It has to be emphasized that an interdisciplinary approach, coordinated by the transplant center, that includes regular skin examinations by a dermatologist is needed to ensure the best care for the OTRs.

Epidemiologic perspectives on immunosuppressed populations and the immunosurveillance and immunocontainment of cancer

  • E. Engels
  • Medicine, Biology
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2019
These epidemiologic observations suggest that there are 2 distinct immune selection processes in humans: immunosurveillance directed against premalignant cells before cancer diagnosis (most relevant for preventing virus‐related cancers), and “immunocontainment” directed against established cancers.



Immunosuppressants and Skin Cancer in Transplant Patients: Focus on Rapamycin

Data suggest that rapamycin could have a protective effect against skin cancer, and new immunosuppressive strategies for transplant patients with skin cancer are not only based on minimizing immunOSuppression.

More epidermal p53 patches adjacent to skin carcinomas in renal transplant recipients than in immunocompetent patients: the role of azathioprine

Investigating whether this drug could increase UV‐induced p53 patches by immunosuppression found no increase, and DNA repair was investigated by ascertaining the effect of azathioprine on unscheduled DNA synthesis (UDS) in UV‐irradiated human keratinocytes.

Molecular Concepts of Virus Infections Causing Skin Cancer in Organ Transplant Recipients

  • I. NindlF. Rösl
  • Medicine, Biology
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2008
A rodent model system useful to examine future strategies in preventing skin tumor formation in immunosuppressed OTR is described and virus‐induced transformation with special emphasis on the function of HPV as an indirect and HHV‐8 as direct carcinogen in the development of NMSC and Kaposi sarcoma.

Use of proliferation signal inhibitors in non-melanoma skin cancer following renal transplantation

The effect of conversion to PSIs in 53 renal transplant recipients developing NMSC after transplantation was generally well tolerated with minimal adverse events reported, and data suggest that conversion from CNIs to PSI may be useful in the management of N MSC following renal transplantation.

Expression of DNA mismatch repair proteins and MSH2 polymorphisms in nonmelanoma skin cancers of organ transplant recipients

Treatment with azathioprine, commonly used in post‐transplant immunosuppressive regimens, results in incorporation of 6‐thioguanine (6‐TG) into DNA, which confers a survival advantage on MMR‐defective cells, which are hypermutable and may therefore contribute to azithioprine‐related nonmelanoma skin cancer, a phenomenon previously demonstrated in transplant‐associated sebaceous carcinomas.

Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation.

The data suggest that the increased risk of skin cancer observed in organ-transplant patients may be as a result of not only systemic immune suppression but also the local inhibition of DNA repair and apoptosis in skin by calcineurin inhibitors.

Effect of cyclosporin A on DNA repair and cancer incidence in kidney transplant recipients.

Triple therapy was associated with impaired PBMC DNA repair and increased cancer incidence and CsA was responsible in large part for the reduction in DNA repair ability found in the in vitro and in vivo studies.

Skin Cancer in Organ Transplant Recipients—Where Do We Stand Today?

Although the threshold of skin cancer necessitating revision of immunosuppression is debated, this measure should be envisaged at the occurrence of the first SCC, or in case of multiple non‐SCC NMSC.