Immune-Boosting Therapy Ineffective for Some with Melanoma


Holistic-Health-Show-with-Dr-Carl-O-HelvieIn a new study presented at the American Society of Clinical Oncology (ASCO) this month researchers concluded that patients failing to respond to treatment using their own immune cells to destroy tumors, called tumor infiltrating lymphocytes, share changes in mechanisms that switch genes on or off in those cells. They said a pattern of “gene dysregulation” causes immune T cells to turn back to an immature state, making them less effective against metastatic melanoma. Immunotherapies ordinarily enhancem, not disrupt, the abiulity of T cells to identify and destroy cancer cells the same way they would an invading virus.

Researchers stated “Our research offers key evidence for genetic and epigenetic dysregulation as a reason these powerful immune therapies fail to work for so many people with widespread melanoma. ” He continued on to say that immune-based therapies in recent decades has increased the number of people  with advanced melanoma surviving longer that 5 years from 10 to 30 percent. However, immunotherapies still fail  and part of the problem is attributed to tumor cells suppressing the T cell populations that enable immunotherapy. Treatment failure was also believed to be related to factors involved in regulating gene activities tied to T cell function and this research looked to that area for study.

Analyzing genes in 24 melanoma patients researchers searched for patterns of changes in the epigenetics, or chemical modification to the DNA code that assist in controling which genes are turned on and which genes are turned off. Researchers goals was to find evidence that might explain the lack of response to immune boosting therapies in such patients.  Researchers found more than 60 epigenetic changes as well as 10 changes in gene activity that were most common to people for whom immunotherapy failed. Many  of the changes were known from previous research to control the process by which immature cells become either CD4 or CD8 immune T cells. Both are essential in immunotherapy The researcher proposes that these changes lead to T cell malfunction.

Thew next study will continue to analyze epigenetics and confirm their findings in larger numbers of people with advanced melanoma. They believe “If our research is confirmed, it suggests that by modifying the genetic or epigenetic alterations we have identified, we can potentially turn treatment non-res0onders into responders and broaden the success that immunotherapies are having against melanoma and other cancers.”  Researchers also say the procedure could have the advantage of being performed in the patients T cells while the cells are grown in the lab and before being injected into the patient, presenting a potentially safe and convenient treatment option.

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