Previously, oncologists did not use immunotherapy for pancreatic cancer because they thought it was useless. Can research prove otherwise?
Pancreatic cancer is the 4th most common cause of cancer death worldwide, mainly due to the inability to detect and diagnose it early, as well as due to the immune suppression that occurs in the tumor’s microenvironment, preventing the body from getting rid of it through its immune mechanisms.
The journal Nature Cancer published a new study on mice at the University of Texas MD Anderson Cancer Center on pancreatic ductal adenocarcinoma (PDAC), which is considered the most common type of pancreatic cancer. This study aims to identify the precise mechanisms of resistance to immunotherapy and understand them to determine effective immunotherapy for pancreatic cancer.
The researchers found that some immune treatments that inhibit T cells and myeloid suppressor cells led to reprogramming the tumor’s immune microenvironment, thereby improving the anti-tumor response in pancreatic cancer and improving survival rates in laboratory models, indicating a potential treatment for human pancreatic cancer.
Two immune proteins, 41BB and LAG, were significantly expressed in tumor-directed T cells. The researchers found that dual treatment with 41BB agonists and LAG3 antagonists was associated with slower cancer progression and improved survival rates in experimental animals compared to single treatments. And because the dual treatment did not eliminate the tumor, the researchers reprogrammed the tumor’s immune microenvironment to increase its sensitivity to immunotherapy by inhibiting CXCR2 in myeloid suppressor cells.
This triple combination of immune compounds led to complete tumor regression and improved survival in 90% of preclinical models and is currently undergoing human clinical trials to translate this research into clinical studies.
Such studies are promising because of the prevailing belief that we cannot use immunotherapy for pancreatic cancer, in the hope that other non-immunogenic cancers will become responsive to combination immunotherapy after appropriate trials.