Machine learning model to predict cancer immunotherapy response

Recently, as a treatment of cancer, immune system based therapy, also known as immunotherapy, is widely used. Immune checkpoints are part of the immune system and they exist to prohibit an immune response from being too strong that it kills normal cells in the body.
Immune checkpoints start working when proteins on the surface of T-cells, a type of immune cells that are developed from stem cells in the bone marrow and have an essential role in the adaptive immune response, recognize and bind to partner proteins on other cells such as tumor cells. When the binding is solid, an "off" signal is sent to the T-cells which can prevent the immune system from attacking the tumor cells.
Immunotherapy treatments called immune checkpoint blockade "blocks" the checkpoint proteins from binding with their partners, hence, prevents the "off" signal from being sent. This allows the T-cells to kill tumor cells.

Immune checkpoint blockade (ICB) has saved the lives of many patients with metastatic cancers. Metastatic cancer is a cancer that has spread from the part of the body where it started (the primary site) to other parts of the body. When cancer cells break away from a tumor, they can travel to other parts of the body through the bloodstream or the lymph system. In the United States, 6% of women have metastatic breast cancer when they are first diagnosed.

Melanoma is a type of cancer that ICB therapy is widely used for the first line treatment these days. The 3-year overall survival for advanced melanoma has increased from 12% before 2010, when standard of care was chemotherapy, to approximately 60% using ICB therapy such as PD-1/PD-L1 inhibitors. PD-1 is a type of immune checkpoint proteins which is expressed on the surface of immune cells such as T-cells. This protein ensures the ability of the body’s immune response. When PD-1 is bound to its partner protein, PD-L1, it helps keep T cells from killing other cells, including tumor cells. Tumor cells often express PD-L1 on their surface, hence they can escape from the immune response. PD-1/PD-L1 inhibitors are a group of immune checkpoint blockade which suppress the activity of PD-1/PD-L1 proteins. When these proteins are blocked, the “off” signals from the immune system are released and the ability of T cells to kill tumor cells is increased. Although the effect of this treatment is significantly evident, the cost of treatment is still quite high and only less than 20% of cancer patients show response to this type of immunotherapy. Therefore, it is crucial that we build a guideline that can aid a patient to have the most beneficial treatment with positive outcomes. An accurate method for pre-therapy identification of patients whose tumors will respond to ICB would be of significant benefit.