Immunosuppressants – use cautiously

Tip #26 Watch Your Medication

 

Use immunosuppressants cautiously – Overview
•These medicines lower the body’s ability to stop cancer from forming.
•Cyclosporin A, a calcineurin inhibitor, is used as an immunosuppressant and increases the skin cancer risk.
•Azathioprine does not appear to result in an increase in skin cancer risk.
•mTOR inhibitors are associated with an even lesser skin cancer risk.
•The effect of immunosuppression on cancer risk is rapidly reversible for some, but not all, cancer types.
•Risk reversal was mainly observed for cancers with a confirmed infectious cause.

 

Immunosuppression

Source: The website of the National Cancer Institute (www.cancer.gov)

Many people who receive organ transplants take medications to suppress the immune system so the body won’t reject the organ. These “immunosuppressive” drugs make the immune system less able to detect and destroy cancer cells or fight off infections that cause cancer. Infection with HIV also weakens the immune system and increases the risk of certain cancers.

Research has shown that transplant recipients are at increased risk of a large number of different cancers. Some of these cancers can be caused by infectious agents, whereas others are not. The four most common cancers among transplant recipients and that occur more commonly in these individuals than in the general population are non-Hodgkin lymphoma (NHL) and cancers of the lung, kidney, and liver. NHL can be caused by Epstein-Barr virus (EBV) infection, and liver cancer by chronic infection with the hepatitis B (HBV) and hepatitis C (HCV) viruses. Lung and kidney cancers are not generally thought to be associated with infection.

People with HIV/AIDS also have increased risks of cancers that are caused by infectious agents, including EBV; human herpesvirus, or Kaposi sarcoma-associated virus; HBV and HCV, which cause liver cancer; and human papillomavirus, which causes cervical, anal, oropharyngeal, and other cancers. HIV infection is also associated with increased risks of cancers that are not thought to be caused by infectious agents, such as lung cancer.


Here are two scientific papers on Immunosuppressants and cancer:

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


Source: PubMed

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 immunosuppressants cancer riskincreases 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 and may relate to other than immunological effects.

Insights may be gained by the multistep skin cancer theory and xeroderma pigmentosum, where defective nucleotide excision repair (NER) results in a cellular mutator phenotype and cutaneous carcinogenesis. This viewpoint assay summarizes current knowledge about the
influence of the most commonly used immunosuppressive drugs in OTRs on DNA repair.
Calcineurin inhibition results in a 200-fold increased skin cancer risk compared with the normal population
and inhibits NER.

The skin cancer risk under azathioprine is threefold less compared with calcineurin inhibitors, which may relate to inhibition of only the last step of NER, i.e. gap filling. mTOR inhibitors do not reduce NER in the global genome and can inhibit the growth of already initiated tumors, which may account for the markedly reduced skin cancer risk compared with calcineurin inhibitors.

We conclude that OTRs may benefit from treatment regimens other than calcineurin inhibitors and speculate that a targeted modulation of calcineurin-dependent signalling may prevent UV-induced tumor formation by enhancing NER not only in OTRs but also in the general population, at least in part.
© 2011 John Wiley & Sons A/S.

 

“Immunosuppression in solid organ transplant recipients is
associated with increased risk of a broad range of cancers”
Cohort study (BMJ)

Effect of reduced immunosuppression after kidney transplant failure on risk of cancer: population based retrospective cohort study

Source: BMJ 2010;340:c570

The effect of immunosuppression on cancer risk is rapidly reversible for some, but not all, cancer types. Risk reversal was mainly observed for cancers with a confirmed infectious cause. Risk of other cancers, especially those related to end stage kidney disease, remained significantly increased after reduction of immunosuppression.


 

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