The role of immunosuppression and

sunlight exposure in cancer formation with post-renal

transplant patients

By: Amanda StevensAdvisor: Dr. Boissonneault

Overview

• Why is this important to me?

• Why should this be important to you?

• Many people in our communities are immune compromised.

• Immune suppression does not discriminate.

Why and How to Immunosuppress?

• One way of becoming immune compromised is by receiving a transplant and then being treated with immunosuppressant drugs to prevent allograft rejection.

• These drugs can give you one of three outcomes:– Therapeutic effect– Undesired consequences of

immunodeficiency– Nonimmune toxicity to other tissues

Undesired consequences of immunodeficiency

• All of the immunosuppressant drugs interfere with body’s ability to survey and destroy tumor cells.

• This leads to an unchecked balance in the body which can produce tumors and cancers.

• One specific cancer that kidney transplant recipients encounter frequently are skin cancers.

27% of deaths occurring at least 4 years post

transplantation were caused by skin cancer!

At 20 years post transplantation, cancer incidence is estimated to be 70% for renal transplant recipients!

This is your natural immune system

Types of immunosuppressant drugs given to RTRs

• Grouped according to their MOA

• Cyclosporine and Tacrolimus– Calcineurin inhibitors– A little over 20 years old

• Mycophenolate Mofetil [MMF] (CellCept®)– Since 1995– Reversible inhibitor of the enzyme inosine

monophosphate dehydrogenase (IMPDH)

Types of immunosuppressant drugs given to RTRs

• Sirolimus and Everolimus– “TOR” Inhibitors– Blocks proliferation

• Azathioprine– Use started more than 30 years ago– Incorporates itself into DNA– Broad myelocyte suppressant

Types of immunosuppressant drugs given to RTRs

• Corticosteroids– Introduced to the transplant community in the 1960’s– Inhibits the expression cytokines such as: IL-1,

IL-2, IL-3, IL-6, TNF-ά, and γ-interferon.• Monoclonal and Polyclonal Antibodies

– OKT3 (Monoclonal) – IgG– Humanized anti-CD25 Monoclonal Ab (Basiliximab

and Daclizumab)– Atgam (Polyclonal) replaced by Thymoglobulin

preparations.• New drugs on the way!!!!• Studies have tried to prove….

This is your immune system on drugs…immunosuppressants that is

To sum up the drugs…

• Berg and Otley did a study and the paper it produced said:– First, agents used during transplantation

themselves may be carcinogenic– Second, by having chronic

immunesuppression this creates a state in which natural surveillance and eradication of precancerous transformations are hindered!

Types of cancers found in RTR

• Some do not occur at an elevated rate: breast, colon, lung, and prostate.

• Some ARE elevated including: esophagus, skin, liver, cervix, bladder, thyroid, and renal cells.

• Focusing now on skin!

Types of cancers found in RTRGeneral Population Renal Transplant

Recipients

Breast, colon, lung, and prostate

Basal Cell Carcinoma

BCC>SCC at 2-4:1

Esophagus, skin, liver, cervix, bladder, thyroid, and renal cells

Squamous Cell Carcinoma

SCC>BCC at 3:2

Melanoma, Kaposi’s sarcoma, Merkel cell carcinoma

Locations of cancer

• SCC and BCC are normally found on constantly sun exposed areas:

–Temples, forhead, lips, auricles, neck, and upper extremities.

Things can look benign….

A squamous cell carcinoma in an RTR.

http://www.captaincutaneum.com/science/squamous/images/squamous_01.jpg

…or really bad…

http://www.aad.org/education/students/_img/ActinicKerNoMelCancer13.jpg (left)

http://www.imr.gov.my/org/CRC/slide57f.jpg (bottom right)

http://www.lib.uiowa.edu/hardin/md/pictures22/dermnet/21_basal_cell_carcinoma_cancer_imiquimod0822057.jpg (top right)

Risk factors for cancer• No single factor can be pinpointed.• Having multiple risk factors will increase the incidence of

skin cancers.• Risk factors include:

– Being an older pt– Duration of immunosuppression– Male– Earlier age of transplantation – Higher dose of immunosuppresion – Genetic predispositions– Having skin types I, II, or II on Fitzpatrick scale– Significant exposure to UV radiation– HPV infection – Lower CD4+ cell counts naturally

Quick Stats• Only 54% of renal transplant patients even

remember getting advice on staying out of the sun.• Of those 54%, only 30% knew why it was important.• 27% of deaths occurring at least 4 years post

transplantation were caused by skin cancer!• The average post-transplant neoplasm appears on

average at approximately 5 years.• Only 5.6% of RTRs used sunscreen on a consistent

basis prior to transplantation.• That number only increased to 36.7% after

transplantation.

What we can do to help!

• Education– Avoid sun exposure– Use sunscreens– Cover up– Avoid “peak hours” (10a-4p)

• Team approach• Primary prevention

– Screenings (tumor markers, Immunoknow Assay, sCD30)

• Early intervention

In conclusion!

• Educate ourselves!

• Educate our pts!

Thanks for your attention!

Thanks Dr. B!

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management. J Am Acad Dermatol 2002; 47: 1-20.• Buell JF, Hanaway MJ, Thomas M, Alloway RR, Woodle ES. Skin cancer following transplantation: The

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