Pancreatic cancer is often detected in late stages due to its location in the body. Tumors grow undetected within the gut and is hidden from physical palpitation. Additionally, minimal symptoms are present during early stages until the tumor becomes large enough to interfere with daily organ function. Unfortunately, there is only a 13% 5-year survival rate for patients with pancreatic cancer. Although survival depends on stage, most patients are diagnosed when the tumor has already metastasized or spread to other locations. Localized pancreatic cancer or early-stage tumors have a higher 5-year survival rate of ~44%. Treatments for localized cancer includes a combination of chemotherapy and possible immunotherapy after tumor resection. However, once pancreatic tumors spread to other organs survival rate severely drops. The standard treatment for late-stage pancreatic cancer is systemic chemotherapy. This approach reduces tumor growth with a goal to prolong survival. Other options include clinical trials with immunotherapy and other treatments that might manage symptoms better. Symptoms include jaundice, abdominal pain, weight loss, and fatigue. Physicians warn of many different risk factors including smoking, diabetes, and obesity. Individuals changing their lifestyle habits to reflect healthy eating and exercise reduces risk of cancer overall.
Different therapies are currently being investigated to improve standard-of-care for patients with pancreatic cancer. Many clinical trials are testing the use of immunotherapy to redirect the immune response onto the tumor. Immunotherapy has become a promising strategy to treat patients with cancer to elicit robust antitumor immunity. Unfortunately, therapy is limited due to tumors evading detection and physical barriers that prevent treatment from reaching the tumor site. However, recent work has identified a way to overcome treatment resistance in pancreatic cancer.
An article in Immunity, by Dr. Katelyn Byrne and others, demonstrate that pancreatic tumors reshape the microenvironment around them by taking control of regulatory immune cells that normally detect cancer. Researchers found that reprogramming these cells sensitizes tumors to immunotherapy and overcomes therapy resistance. Byrne is an Assistant Professor of Cell, Developmental and Cancer Biology at the Oregon Health & Science University (OHSU) Knight Cancer Institute, School of Medicine. Her work focuses on immunobiology and how the immune system regulates therapeutic sensitivity to cancer.
Byrne and her team used mouse models to test the role of CD40, a surface molecule on immune cells. Researchers activated CD40, which is upstream to most signaling pathways that elicit an immune response. Through CD40 stimulation, researchers found that they can generate a robust immune response. It not only activated antitumor immune cells, but it reprogrammed regulatory T cells to support antitumor function. This unexpected discovery was the result of off-target effects and allow other immunotherapies to have a strong effect on pancreatic tumors.
This discovery helps explain why immunotherapies haven’t worked in the past. These findings make it possible to give patients a combination of treatments that might have stronger effects and reduce tumor growth. As a result, combination therapy using a CD40 agonist has the potential to improve patient survival. These approaches also offer an opportunity to personalize treatment strategies by administering combination regimens specific to a patient. Overall, Byrne and others have discovered a unique therapeutic target that has the potential to enhance current standard-of-care therapy.
Article, Immunity, Katelyn Byrne, OHSU, Knight Cancer Institute