OPRM1 AND CD8+ T-CELL SPATIAL DISTRIBUTION IN ADVANCED CUTANEOUS MELANOMA

Immunotherapy has greatly improved treatment for people with advanced cutaneous melanoma, but many patients either do not respond or stop responding over time. One important reason for this failure is that the body’s immune cells are unable to reach and attack the cancer. In some melanomas, cancer-fighting CD8 T cells are present near the tumor but remain stuck outside the cancer cell clusters instead of entering them. This pattern, known as immune exclusion, is linked to poor responses to immunotherapy, yet the reasons it occurs are not well understood.

This project focuses on a gene called OPRM1, which produces the mu-opioid receptor. While this receptor is best known for its role in pain control, recent research suggests it may also influence how the immune system behaves in cancer. Laboratory studies show that opioid signaling can weaken immune responses against tumors, and blocking this pathway may help immune cells function more effectively. However, in human melanoma, it is not known whether OPRM1 plays a role in keeping immune cells away from cancer cells.

Using stored tumor samples from patients with advanced melanoma, this study will examine where immune cells are located in relation to melanoma cells and measure OPRM1 levels within the tumor. Advanced imaging methods will allow us to determine whether tumors with higher OPRM1 expression are more likely to keep immune cells at a distance from the cancer.

By identifying a possible biological reason why immune cells fail to reach melanoma tumors, this research aims to improve understanding of immunotherapy resistance and support the future development of treatment strategies that help the immune system more effectively target melanoma, particularly for patients with limited remaining options.