Melanoma has a higher likelihood than many other cancers of spreading to the brain. Once it spreads to the brain, current immunotherapies often do not work.
A team of Yale researchers believes that preventing the spread may rely on the brain's immune system, not just the tumor itself.
“Melanoma is one of the malignancies with the highest propensity to ‘home’ to the brain,” says Nelson LaMarche, PhD, assistant professor of pathology. “And once melanoma cells metastasize to the brain, this disease is notoriously difficult to treat. While current immunotherapies have revolutionized treatment for melanoma, a substantial amount of brain metastases do not respond.”
LaMarche, whose lab is part of the Yale Cancer Biology Institute on West Campus, is leading a team of Yale researchers focused on immune cells present in the brain before the skin cancer spreads. These cells may help establish the cancer's initial presence in the brain.
LaMarche is working with Harriet Kluger, MD, Harvey and Kate Cushing Professor of Medicine (Oncology) and of dermatology, and Lucia Jilaveanu, MD, PhD, assistant professor of medicine (medical oncology). Kluger is an expert in combination immunotherapies for melanoma, and has conducted extensive studies on brain metastases. Jilaveanu is an expert on preclinical models of melanoma brain metastasis and leads studies of the disease’s brain adaptations.
Their project will focus on identifying myeloid-focused strategies for preventing melanoma brain metastasis and determining whether blockade of the IL-4 axis is an effective intervention to prevent the disease from spreading. The IL-4 axis is a critical signaling pathway that regulates inflammation, allergy, and tissue repair, but its overactivation can lead to cancer immunotherapy resistance.
This work is supported by a Department of Defense Melanoma Research Program Team Science Award. The grant supports two or three independent investigators in conducting multidisciplinary, high-risk/high-gain research to accelerate melanoma prevention, treatment, and survivorship solutions. The federal agency funds the award because military personnel face significantly higher risks of developing melanoma due to prolonged sun exposure during service.