HLA Antigen Matching Linked With Skin Cancer Risk After Heart, Lung Transplants

By David Douglas

February 01, 2019

NEW YORK (Reuters Health) - Rates of de novo skin cancer after lung or heart transplantation are higher when donor and recipient HLA antigens are well matched, a large retrospective study suggests.

Lung and heart recipients with HLA mismatches "actually had less skin cancer than those with a closer match," Dr. Sarah T. Arron told Reuters Health by email. "This suggests that the immune system of patients with mismatches may still be able to recognize and fight off skin cancer cells despite the high level of immunosuppression required to protect the transplanted organ."

"Internists and dermatologists who treat organ transplant recipients should be aware that the risk of skin cancer may be higher in patients who underwent thoracic transplant and received a well-matched organ," Dr. Arron of the University of California, San Francisco, and colleagues write in a January 23 online paper in JAMA Dermatology.

They note that immunosuppressive regimens that reduce the risk of graft rejection increase the risk of cancer, a major source of morbidity and mortality in solid-organ transplant recipients.

Molecular mechanisms play an important role in the defense against the development of cancer, but "data on the association between HLA antigen mismatch and skin cancer incidence are limited, and kidney transplant recipients have been the focus," they add.

To investigate further, the team examined data on more than 10,600 recipients of lungs, hearts, pancreata, livers, and kidneys between 2003 and 2008. The study, which was conducted between 2016 and 2017, matched participants to skin cancer outcomes by medical record review.

"A greater number of mismatched alleles, as identified through the standard antigen mismatch and broad specificity mismatch methods, was associated with a protective effect," the researchers report.

In particular, a 7% to 8% reduction in skin cancer risk was found for each additional mismatched allele. Subgroup analysis showed that HLA antigen mismatch led to significant protection in lung recipients (adjusted hazard ratio, 0.70 ) and heart recipients (aHR, 0.75), but not for those who received a liver, kidney, or pancreas. The degree of HLA-DR mismatch was the most statistically significant for skin cancer risk (aHR, 0.85).

"The aHRs for squamous cell carcinoma and melanoma were similar to those for any skin cancer, but the HR was not statistically significant for melanoma because of the smaller number of events," the researchers report.

In light of these findings, they conclude that "well-matched heart and lung transplant recipients may have a higher risk of skin cancer after transplant." And, added Dr. Arron, "Future studies are still needed to learn how different immunosuppressive drugs impact this finding."

Commenting by email, Dr. Mark Faries, Co-Director of the Cutaneous Oncology Program and Professor of Surgery at Cedars-Sinai Medical Center, Los Angeles, told Reuters Health, "The immediate implication is that for heart or lung transplant patients, the risk for skin cancers is going to be highest for patients with the best matches. Over the long term, this research may lead to identification of the mechanisms at work for the patients with poor matches that protect them from skin cancers, and perhaps new therapies."

SOURCE: http://bit.ly/2MFliAU

JAMA Dermatol 2019.