In cancer cells, there are different ways to resist chemotherapy, radiation therapy and other treatments. Researchers at Mayo Clinic have deciphered one of these methods, using cell lines and tumor cells derived from patients.
Cells on the outer surface there are proteins that provide information to the body. In some cancer cell protein PD-the L1 binds to PD-1 protein on the surface of immune T cells. The T-cell PD-1 acts as a brake immune response. When the L1 and PD-1, PD-connected, T-cells receive a message stating that the cell to which they are attached, is a normal, and the immune response is not required. Tumor cells use elevated levels of PD-L1 on their surface. Today drugs intended for these control points, are among the most promising types of cancer immunotherapy.
In a new publication, a team of researchers from the Mayo Clinic talks about how PD-L1 helps cancer cells.
«PD-L1 helps cells become resistant to chemotherapy and radiation therapy, - says Chzhenkun Lu, one of the leaders of Experimental Therapeutics Program in Oncology Center. -Our data suggest that cancer cells with high levels of PD-L1 can be more resistant to standard radiotherapy and chemotherapy. "
The team also reported that the antibody used in their studies, blocking the function of the internal PD-L1, making the cells more sensitive to treatment.
Haydong Dong, MD, cancer immunology, has long been studying cell surface protein. Since management of FDA by the Food and Drug Administration approved anticancer medicament for blocking the PD-L1 or PD-1, a laboratory sought marker or an antibody that would bind to these proteins, and would indicate which patient will benefit from this form of immunotherapy.
"My laboratory has developed several lines of antibodies to PD-L1, and at the same time, we tested whether the chemotherapy will increase the expression of PD-L1 or not, - says Dr. Dong. - We have noticed that the tumor cells without PD-L1 showed an increased sensitivity to a particular chemotherapy, which causes DNA damage. But the underlying mechanism was not clear. "
Dr. Lu and Dr. Robert Mutter attempted to identify potential molecular mechanism responsible for resistance to cancer therapy which causes DNA damage in cancer cells. Dr. Lu spent examination of DNA damage at the molecular level. Robert Mutter, MD, provided expertise in the field of DNA repair, the biology of breast cancer and the use of DNA therapy in the clinic to improve treatment results of patients with refractory breast cancer. Researchers have tried to find out why the tumor cells, which have more PD-L1, were particularly resistant to DNA damage.
They found that in PD-L1 cells were used to accelerate recovery during chemotherapy or radiation therapy. This article was first reported about a new feature PD-L1 as an RNA-binding protein. PD-L1 can protect certain RNA which encode important proteins required for recovery of tumor cells. They also report that H1a, one of the antibodies designed to attach to PD-L1, PD-L1 destroys part of the protein, which helps it to maintain its function in cancer cells.
"For cells of breast cancers that express PD-L1, we can use H1A antibody to make these cells more sensitive to treatment," - says Dr. Lu.
The researchers hope that they will improve the results of treatment of patients with refractory cancer.