The role of aging in immune-regulated reactivation from metastatic melanoma
Description: Melanoma is the deadliest form of skin cancer. It is deadly when it spreads from the skin to other parts of the body, a process known as metastasis. Most patients are not completely cured with current melanoma treatments, as cancer cells can go into a dormant state within organs, where they are alive but are no longer growing. Dormant cancer cells are hard to detect and resistant to the treatments that use the body's immune system to destroy cancer. Understanding how dormant melanoma cells become active again to form large tumors throughout the body, interact with the surrounding tissue, and avoid immune attack is critical to improve melanoma treatment.
We previously discovered that the age of the host organism determines when dormant melanoma cells grow again. In young mice, melanoma cells in the lungs are dormant and unable to grow. Aging of the lung provides signals to the melanoma cells to 'reactivate' from dormancy and form large metastatic tumors which cause death. We showed that the receptor in melanoma cells, MER, promotes this reactivation from dormancy, whereas the receptor AXL maintains dormancy in melanoma cells. Both receptors are critical for metastases to form in the lung which ultimately causes patient death.
We are now able to expand on our previous studies and investigate how the immune system promotes dormancy or reactivation with age. We will also study how melanoma can metastasize differently to multiple organs such as the liver and lung. This proposal will use new ways to directly form metastases in the lungs and livers that can be directly compared with tumors in the skin. We will determine how aging alters tumor growth across these different tissue sites and how it alters response to treatments that activate the immune system against melanoma. We will use a drug that blocks both AXL and MER function to target both dormant and reactivated cells to determine if it improves the effects of current melanoma treatments against metastases.
Funder: Melanoma Research Alliance
Amount: $255,000
Funding type: award
Start date: 2024-06-01
End date: 2027-05-31
Investigator: Mitchell Fane
Institution: The Research Institute of Fox Chase Cancer Center
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: 1258843
OpenAlex ID: G3485836293