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April 18, 2018 | 3 minute read

Scientist in the Spotlight: Dr. James Fleet

Immunotherapy works by stimulating a patient’s own immune system to fight and destroy cancer cells. However, many patients do not respond optimally to this treatment method. Experts say immunotherapy is ineffective in these cases because the tumor cells are not recognized by the immune system as foreign. Dr. Fleet and his team hypothesize that low vitamin D status alters the immune system in ways that enable tumors to escape immune surveillance. With AICR’s support, Dr. Fleet’s team is examining the connection between low vitamin D signaling and immunotherapy. Read his interview with AICR.

Q: What is immunotherapy? How does it impact the current face of cancer treatment?
A: Immunotherapy is a new form of cancer treatment that stimulates the immune system.  We generally understand that our immune system attacks infections caused by external agents, but actually, the immune system also recognizes and kills our own cells when they are damaged.  Often, the immune surveillance can recognize cancer cells as foreign because cancer-causing mutations make the cell produce abnormal proteins.   When that happens then the immune cells can recognize and clear cancer cells from the body. However, we have learned that some cancers can be recognized by the immune system and others are hidden from it.   Immunotherapy stimulates the immune system and makes it better in finding the hidden cancer cells. It is also important to point out that immunotherapy does not work for all types of cancer and for all people. However, when it works, it works well.
Q: How is immunotherapy different from other cancer treatments?
A: Most cancer treatments involve chemicals that target the cancer cell and kill them or they deactivate some essential function of the cancer cell that it needs to survive.   Immunotherapy works indirectly by acting on a different cell within the tumor environment – a type of cell called T cell.  It stimulates the T cell to attack the tumor cell.   Sometimes immunotherapy works alone but sometimes it is used along with a traditional tumor cell-killing therapy.
Q: According to your preliminary hypothesis, what is the role of Vitamin D in immunotherapy?   
A: One of the reasons why some tumor cells are not recognized by the immune system as foreign is because the tumor fools the immune system.  The tumor produces factors that recruit and activate a special type of immune cell called the myeloid-derived suppressor cell or MDSC.  This cell protects the tumor by suppressing the function of the T cell that would ordinarily attack the tumor.   We have found that the active form of vitamin D can block the function of the MDSC.   We hypothesize that by “suppressing the suppressor” vitamin D allows T cells to attack the tumor.   It is important to clarify that we do not think Vitamin D is a replacement for an immunotherapy drug.   Instead, we think that it may help immunotherapy drugs work better by removing a barrier that could limit their success.
Q: Some consider immunotherapy to be a “miracle” cure. What do you want people to know about immunotherapy?
A: I think that people need to understand that cancer is not a uniform disease.  As a result, different cancers respond to different therapies.   Immunotherapy is part of a growing arsenal of approaches that doctors can use against cancer.

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