Approved research

Single nucleotide polymorphisms associated with PD-1 inhibitor treatment response in stage III melanoma patients

Lay summary

Under normal physiologic conditions, non-cancerous cells in the body have a protein on their surface called PD-L1 that binds to a receptor on the surface of T-cells of the immune system called PD-1. This interaction causes suppression of activated T-cell activity after an infection has been cleared to prevent other healthy cells of the body from being harmed by the immune system. Cancerous cells, such as those that make up a melanoma, can also express PD-L1 on their surface that can prevent immune cells from fighting the tumor. PD-1 inhibitors are used in the treatment of melanoma to prevent the interaction of PD-L1 on tumor cells with PD-1 on T-cells. By preventing this interaction, T-cells are not suppressed and an immune response to the tumor is promoted. Although inhibition of the PD-1 checkpoint in advanced stage melanoma treatment induces a high rate of anti-melanoma response, clinical use is limited by a high rate of innate resistance. Consequently, PD-1 inhibitors do not help 40-45% of patients and research suggests that properties of the tumor itself are not the only reason why some patients do not respond to the treatment. We are aiming to look at patients' normal germline DNA to determine if there is an association between single nucleotide polymorphisms, or variations in the DNA, and response to treatment. If differences in a patients' normal DNA play a role in how effective PD-1 inhibitors are in treating their melanoma, we may be able to predict if the treatment will be effective without a trial of the medication. This could save resources and allow doctors and patients to choose other treatment options to which patients may respond. The project duration is expected to take no longer than 12 months.