The Aging Microenvironment Is A Determinant Of Immune Exclusion And Metastatic Fate In Pancreatic Cancer
Aging is a major risk factor for many diseases, including pancreatic cancer, a particularly aggressive form of the disease. While we know there’s a strong link between age and pancreatic cancer outcomes, traditional research models haven’t fully captured the complex biological changes that occur in older individuals.
This new research utilized more age-relevant models to investigate how aging affects pancreatic cancer progression. The findings revealed that as an organism ages, the progression and spread (metastasis) of pancreatic cancer accelerate.
The key to this acceleration lies not just within the cancer cells themselves, but in the “tumor microenvironment” – the complex network of cells, blood vessels, and molecules surrounding the tumor. Specifically, the study focused on “cancer-associated fibroblasts” (CAFs), which are cells that help form the structural framework of the tumor.
Researchers found that in older tumors, these CAFs exhibited a distinct genetic signature related to the extracellular matrix, which is the material that provides support and structure to cells. This altered environment in aged tumors was linked to a weakened immune response against the cancer and a greater tendency for the cancer to spread.
In a remarkable experiment, the scientists demonstrated that by introducing young CAFs into the aged tumor environment, they could essentially “rejuvenate” the surrounding tissue. This revitalization led to an improved immune cell infiltration into the tumor and a reduction in metastasis in older hosts. Conversely, aged CAFs did not enhance metastasis in young hosts, suggesting that a youthful microenvironment can exert a dominant control over disease progression.
These findings highlight that the age of the tumor’s surrounding tissue is a crucial factor in how pancreatic cancer behaves. This new understanding opens exciting avenues for developing therapies that specifically target the aging components of the tumor microenvironment to improve outcomes for patients, especially older individuals battling this challenging disease.
Source: link to paper