While immunotherapy has shown great promise in other solid tumors, such as lung cancer and melanoma, checkpoint inhibitors have not been successful thus far in pancreatic cancer.
Challenges of immunotherapy
This lack of success is believed to mainly be due to the general lack of neoantigens and the immune-suppressive tumor microenvironment (TME). The TME is composed of extracellular matrix (ECM), fibroblasts, and endothelial and hematopoietic cells, mainly of the myeloid lineage. Most immune-infiltrates are largely devoid of cytotoxic effector T-cells due to myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) contributing to local immunosuppression.
We envision a three-pronged approach, including chemotherapy or radiation to kill the tumor cell and release tumor antigens, depletion or reprogramming of myeloid suppressor cells to relieve local immune-suppression, and recruitment/augmentation of T-cell responses. We expect that a combination of immune-related agents will become an effective therapy in the future.