PD-1/PD-L1 Blockade: A New Promising Therapy for the Treatment of Pancreatic Cancer.
Programmed cell death protein 1, a member of the CD28 family, is an immune-checkpoint receptor expressed on
a variety of immune cells, such as T-cells, monocytes, B-cells, dendritic cells, and tumor-infiltrating lymphocytes.
PD-1 major role is to limit the activity of T-cells in peripheral tissues at the time of an inflammatory response to
constrain autoimmunity and tissue damage. Engagement of PD-1 by one of its two known ligands inhibits kinases involved in immune cell activation. Interestingly, PD-1 has an opposite function in Treg lymphocytes.
In the tumor microenvironment, PD-1/PDL1 axis represents one of the mechanism utilized by tumor cells to avoid immune surveillance. Many different tumors express high-level of PD-L1
including breast, urothelial, ovarian,
cervical, colorectal, gastric, pancreatic, and non-small-cell lung cancer, melanoma, and glioblastoma.
PD-L1 is also expressed
on tumor-infiltrating dendritic cells and macrophages. PD-L1+
cells are able to induce T-cell apoptosis protecting tumor cells from
being killed T-cells and interfering with PD-1/PD-L1 axis is described to reactivate the immune response against cancer.
Immunotherapy with monoclonal antibodies targeting PD-1 or PD-L1 represents a powerful
weapon in the oncology
field. Clinical studies demonstrated that this type of therapy exerted benefits in different types of cancers.
Durable objective (partial or complete) responses following anti-PD-1 therapy in patients
with advanced melanoma (31-44% of patients), non-small-cell
lung cancer (NSCLC; 19-20%) and renal cell carcinoma
(RCC; 22-25%).
Pancreatic ductal adenocarcinoma is a highly
lethal human cancer, with a 7% 5-year overall survival rate, and
represents the fourth leading cause of cancer-related deaths in the
USA.
Pancreas Open J. 2018; 2(1): e5-e7. doi: 10.17140/POJ-2-e007