MAR 11, 2016 8:14 AM PST

Macrophages Break Down Protective Barrier of Pancreatic Tumors

WRITTEN BY: Kara Marker
In 2016, the five-year survival rate for pancreatic cancer increased from seven to eight percent (American Cancer Society). Not a monumental increase, but scientists are still working on therapies to get the numbers even higher.

Scientists from the Abramson Cancer Center University of Pennsylvania School of Medicine, in their new preclinical study published in the journal Cancer Discovery, investigated the potential of macrophages to break down protective walls around pancreatic tumors, also known as their microenvironment. They found that sending certain signals to macrophages with an experimental immune therapy can be successful in influencing them to strip away the protective parts that pancreatic tumors use to evade the harsh chemicals of chemotherapies.
 


“We’ve learned how antibodies that target a cell surface molecule called CD40 work with the immune system to tear back that wall,” said study leader Gregory Beatty, MD, PhD. Plus, the same antibodies were found to actually enhance the effect of chemotherapy once the tumor’s defenses were stripped away.

The ACC study recently published followed a previous study by the same researchers. In 2011 they illustrated the ability of CD40 to prompt monocyte and macrophage populations to destruct the tumor microenvironment. However, until their newest study, the team couldn’t pinpoint the precise mechanism behind the connection between CD40 and the immune cells.

Their new study involved mouse models of pancreatic cancer, and they were able to identify two immune factors released after CD40 antibody treatment. The suspects are chemokine ligand 2 (CCL2) and interferon gamma. While CCL2 recruits macrophage tumor infiltration, interferon-gamma prompts macrophages to release enzymes called metalloproteinases, which degrade the “fibrotic scaffold” of the tumor microenvironment, the structure that protects the cancerous cells from destruction by chemotherapy.

The tag team effort of CCL2 and interferon-gamma, as a result of CD40 antibody stimulation, leads to fibrosis degradation, identified by the scientists as the final blow in breaking down the tumor defenses.

While this discovery is promising in the fight against pancreatic cancer, the research team also realized that the timing of CD40 treatment followed by chemotherapy is extremely critical: too soon and patients are at risk for a 30 percent mortality rate, and too late and the chemotherapy is ineffective. They found that the “sweet spot” for chemotherapy delivery is five days post-CD40 treatment, where they saw the treatment well-tolerated and tumor cells shrinking and dying.

“Macrophages can be very potent killers of cancer,” Beatty said. “Since keeping them out of tumors is a challenge, why not harness their recruitment?”
 

Source: University of Pennsylvania School of 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.
You May Also Like
DEC 15, 2020
Immunology
Immunity-Boosting: Is It Real?
DEC 15, 2020
Immunity-Boosting: Is It Real?
The question everyone tries to find an answer to in the winter season is how can we improve our immunity to fight any in ...
DEC 28, 2020
Immunology
What Happens When Your Immune System Works Against You?!
DEC 28, 2020
What Happens When Your Immune System Works Against You?!
Our immune system is our army against any molecule that wants to invade our bodies like viruses, bacteria, and cancer. I ...
JAN 19, 2021
Immunology
How Breastfeeding improves Infants Immunity?
JAN 19, 2021
How Breastfeeding improves Infants Immunity?
Breastfeeding benefits are well known for ages, and it has many positive impacts on infant's lives that continue wit ...
MAR 04, 2021
Immunology
Why Do We Need Two Shots of the COVID Vaccine?
MAR 04, 2021
Why Do We Need Two Shots of the COVID Vaccine?
Unlike social distancing, mask-wearing, and hand hygiene, vaccines are our best bet as a long-term solution to protectin ...
APR 20, 2021
Immunology
Scientists Map the Genetic Landscape of COVID Infections
APR 20, 2021
Scientists Map the Genetic Landscape of COVID Infections
Scientists have identified 65 human immune genes activated during SARS-CoV-2 infection. This finding provides valuable i ...
APR 27, 2021
Neuroscience
Leaky Blood-Brain Barrier Linked to Schizophrenia
APR 27, 2021
Leaky Blood-Brain Barrier Linked to Schizophrenia
Researchers from the University of Pennsylvania have found that people with schizophrenia may have a more permeable bloo ...
Loading Comments...