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Immune Dysfunction, Age Lower Survival Odds

CancerWise - July 2008

Elevated levels of an immune system protein called interleukin-12 (IL-12) predict poor survival prospects for people with advanced melanoma, particularly for older people, researchers reported at the annual meeting of the American Association for Cancer Research in June.

Significance of results

"Melanoma in some cases can be vulnerable to attack by a patient's immune system," says senior researcher Jeffrey E. Lee, M.D., professor in M. D. Anderson's Department of Surgical Oncology. "What we've found could be evidence of a dysfunctional immune response that actually fuels the growth of melanoma."

Research methods

The general level of a person's immune function declines with age, as do the levels of many cytokines, like IL-12, that are vital to immune system function. IL-12 is a cytokine that tells cells and other proteins what to do and can assist the immune system in destroying tumor cells.

In the study, the research team examined 658 melanoma patients.

Those participants had different stages of the disease:

Stage I and II – There were 445 patients with a diagnosis of stage I or II melanoma, which is also called localized melanoma (cancer that has not spread to the lymph nodes).

Stage III – There were 150 participants with stage III melanoma (cancer that has spread to the lymph nodes).

Stage IV – There were 63 patients with stage IV melanoma (cancer that has spread to distant organs).

Researchers analyzed participants’ age, stage of disease and blood level of IL-12. After following the patients for an average of 13 months, they correlated IL-12 levels with patient outcomes and survival.

Primary results

Poor overall survival was associated with either higher:

  • Age
  • Stage of disease
  • Blood levels of IL-12

Among patients with stage III melanoma, those with the highest levels of IL-12 had a risk of death nearly five times higher than other patients.

Additional results

The study confirmed that IL-12 levels generally increase with age.

Although older stage III patients had an elevated risk of death, age alone did not play a part in whether patients survived the disease.

The association between IL-12 and advanced age could help explain the link between age and poorer prognosis in melanoma. Elevated IL-12 may be a marker of an immunosuppressive, tumor-promoting response in melanoma patients.

What’s next?

IL-12 is already targeted by therapies used to treat autoimmune diseases, Lee says.

“Preliminary results of our study suggest that ultimately blocking IL-12 could be of benefit to melanoma patients. However, we are currently examining the relationship of 30 different cytokines, including IL-12, with age and outcome in melanoma patients. Our goal is to help determine which represent the best blood markers of recurrence and which will be the best targets for new therapies.”

— Adapted by Dawn Dorsey from an M. D. Anderson news release

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© 2014 The University of Texas MD Anderson Cancer Center