A method of determining risk for skin cancer development and skin cancer therapeutic prevention by measuring pd-1/pd-l1 signaling pathway members

An in vitro method for determining a risk of developing skin cancer in a sample, the method comprising:

• a) measuring expression of family, regulatory, and/or downstream signaling member(s) of programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) pathway in a non-irradiated skin sample;
• b) measuring expression of family, regulatory, and/or downstream signaling member(s) of PD-1/PD-L1 pathway in an irradiated skin sample taken in close proximity to location of non-irradiated skin sample;
• and
• c) determining risk of developing cancer in said skin sample based on a difference in said measured expression of family, regulatory, and/or downstream signaling member(s) of PD-1/PD-L1 pathway between said non-irradiated sample and said irradiated sample, wherein said difference in expression comprises at least 5% determines risk of developing skin cancer in said sample.

A method for preventing development of skin cancer in a subject at risk for developing skin cancer, the method comprising:

• a) measuring expression of family, regulatory, and/or downstream signaling member(s) of programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) pathway from a first tissue sample obtained from a region of interest or an area suspected of developing skin cancer prior to applying UV radiation to said region of interest of said subject, wherein said first tissue sample is not irradiated or a non-irradiated tissue sample;
• b) measuring expression of family, regulatory, and/or downstream signaling member(s) of PD-1/PD-L1 pathway in a second tissue sample obtained from said region of interest after applying UV radiation to said region of interest of said subject, wherein said second tissue sample is irradiated or an irradiated tissue sample;
• c) determining said risk of developing skin cancer in said subject based on a difference in said measured expression of family and/or regulatory member(s) of PD-1/PD-L1 pathway between non-irradiated and irradiated tissue samples, wherein said difference in expression comprises of at least 5% determines a risk of developing skin cancer;
• and
• d) determining a management strategy to prevent development of skin cancer in said subject based on determined risk of developing skin cancer, wherein said management strategy comprises administering drug(s) that alter PD-1/PD-L1 signaling or expression, drugs that are used to treat skin cancer, and/or drugs for therapeutic prevention, recommending lifestyle changes, additional and/or more frequent monitoring or assessment, and/or implementing alternative interventions or prophylactic treatments thereof to said subject.