Engineering NK Cell–Mediated Stromal Remodeling to Reprogram the Tumor Microenvironment in Immunocompetent PDAC Models
Posted in Announcements
by Marwa Afifi, BDS, MDS, PhD
Pancreatic cancer is one of the most difficult cancers to treat. Killing and targeting tumor cells alone is no longer enough, as survival rates remain dismal even after decades of tumor cell-killing chemotherapy.
Pancreatic cancer is one of the most difficult cancers to treat. Killing and targeting tumor cells alone is no longer enough, as survival rates remain dismal even after decades of tumor cell-killing chemotherapy. Furthermore, immunotherapy, which has worked in other cancers, does not work well in pancreatic cancer. In large part, this is because immune cells simply cannot reach the pancreatic tumor cells to kill them.
This is because pancreatic tumors are surrounded by a dense, scar-like tissue called the desmoplastic stroma. This stroma acts like a physical wall, protecting the tumor cells and preventing immune cells from getting in. As a result, even if the immune system is activated, it cannot effectively access or eliminate the cancer.
Allowing immune cells to reach the cancer
Our work focuses on remodeling this dense stroma that supports and surrounds tumor cells. Instead of targeting only the cancer cells, we are engineering natural killer (NK) cells, a type of immune cell, to release enzymes that can break down this dense wall of scar tissue and eat it away. Essentially, the goal is to open up the tumor and allow immune cells to reach and attack cancer cells.
What is next?
We aim to test whether this approach can overcome this physical barrier and improve immune cell access and function within the tumor. More importantly, we see this as a strategy that can be combined with other tumor-targeted therapies, since combination approaches are likely the future for treating aggressive cancers like pancreatic cancer.
Why this is important
If successful, this work could help overcome one of the major limitations in treating pancreatic cancer and lead to better outcomes for patients, where survival is currently often measured in months rather than years.
This work needs support
Very recently, we won free Lombardi Shared Resources support for this project, which will facilitate our experiments and bring us closer to improving treatment efficacy for patients with pancreatic cancer.