APR 12, 2017 6:42 PM PDT

Pancreatic Cancer Cells and Their Immune Invisibility Cloak

WRITTEN BY: Kara Marker

Pancreatic ductal adenocarcinoma (PDA) usually kills those diagnosed within five years, due to the ability of pancreatic cancer cells to manipulate cell signaling among immune system cells to their advantage. A new study finally uncovered the molecular mechanisms behind this manipulation, highlighting a new option for anti-cancer therapies.

Credit: Spandidos Publications

High levels of two interacting proteins, dectin-1 and galectin-9, are observed in high levels found in both mice and human cancer. The communication between these two proteins prevents immune cells called macrophages from killing cancer cells, and past studies link high levels of galectin-9 to reduced survival in PDA.

How do they do it? Pancreatic cancer cells release signals that influence the maturation of macrophages, which can become either M1 or M2, cancer-attacking or immune-suppressing, respectively. The immune system typically recognizes cancer cells as needing to be attacked, but pancreatic cancer cells’ signals cause precursor macrophages to become M2 as opposed to M1.

"Pancreatic cancer cells are deadly because they program nearby immune cells to permit the tumors to survive and grow," explained study author George Miller, MD.

Essentially, signals received by  receptors on the surface of both types of macrophages are intercepted by pancreatic cancer cells. These cells then send signals to macrophages to make abnormal amount of dectin-1 surface receptors and follow up by producing enough galectin-9 to match, creating an army of M2 macrophages to suppress the immune system, allowing the tumor to grow uninhibited.

From the New York University School of Medicine, researchers developed a mouse model of PDA to understand the relationship between macrophage maturation and signals released by cancer cells. One group of mice, genetically altered to not make dectin-1, lived longer than a normal group. Also, treating mice with an antibody blocking the reaction between galectin-9 and dectin-1 reduced tumor size and increased survival times. Lastly, treating mice with an antibody that prevents galectin from interacting with dectin on the surface of macrophages caused them to become M1 instead of M2.

In addition to shifting the ratio of M1 to M2 macrophages in favor of the immune system, producing more M1 macrophages resulted in the recruitment of cancer-killing T cells.

“Macrophages with dectin-1 on their surfaces and cells expressing galectin-9 infiltrate many cancer types," said Donnele Daley, MD, explaining how the present study’s results could have broad implications beyond just treating pancreatic cancer.

The new study’s results have the potential to lead to drug targets for use in combination with checkpoint inhibitors, a form of cancer immunity therapy that has been unsuccessful in treating pancreatic cancer.

Sources: NYU Langone Medical Center / New York University School of Medicine, Nature Medicine

About the Author
I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
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