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Understanding what goes wrong in the immune system — and how to set it right again
Understanding the immune system is key to understanding how to better treat and prevent cancer.
When they’re working optimally, our immune systems regularly detect and eliminate pre-cancerous cells. But cancer has many ways to evade and subvert normal immune responses and sometimes slips past these many-layered control systems. Researchers at the Allen Institute for Immunology are working to uncover the immunological malfunctions that underlie the blood cancer multiple myeloma and the skin cancer melanoma.
Multiple myeloma is a cancer of a bone marrow cell known as a plasma cell, the precursor to all our blood and immune cells. This blood cancer affects around 35,000 people in the U.S. each year and kills nearly 13,000. In some patients, the tumor begins slowly and may smolder at a low level for some years before it progresses. Current treatments for multiple myeloma have improved survival but the relapse (or recurrence) rate for the tumor is high, and 5-year survival is still only around 50%.
Scientists don’t yet understand how multiple myeloma — itself a cancer of immune cells — affects the immune system overall, nor how the disease can survive at low levels in the body for years without recognition by healthy immune cells.
Researchers at the Allen Institute for Immunology are partnering with teams at Fred Hutchinson Cancer Center to better understand what happens to the immune system in patients with multiple myeloma as they undergo treatment. They are studying a particular myeloma treatment called an autologous stem cell transplant, a bone marrow transplant that uses the patient’s own healthy blood cells to replace the cancerous cells. Through their research profiling patients’ immune systems in great detail, the teams will ask whether this kind of transplant “resets” the immune system in multiple myeloma patients and will look for the specific tricks the cancer uses to sabotage the immune system’s normal cancer surveillance. These research avenues could identify new types of treatment for this blood cancer.
The skin cancer melanoma is a cancer of the pigment-producing cells in the skin and is one of the rarer but more deadly forms of skin cancer. Nearly 100,000 people in the U.S. are diagnosed with melanoma every year, making up only about 1% of all skin cancer cases in this country. Around 8,000 people die of melanoma every year, by far the majority of skin cancer-related deaths.
In recent years, a form of cancer immunotherapy known as checkpoint inhibitors has revolutionized the treatment of melanoma. Checkpoint inhibitors are drugs that release the “brakes” on a kind of immune cell called a T cell, allowing it to attack cancer cells more aggressively. While these drugs have improved outcomes for many melanoma patients, they don’t work for all. The drugs also increase risk of autoimmune disease, since they release the brakes on all T cells, not just those that recognize cancer.
Our scientists are working with researchers at the University of Pennsylvania to better understand how checkpoint inhibitors work in the context of melanoma, and how these drugs might lead to autoimmune disease.