Aggressive Nature of Pancreatic Cancer Linked to Infighting Among Immune Cells

Aggressive Nature of Pancreatic Cancer Linked to Infighting Among Immune Cells

A specific type of T-cell, called gamma delta T-cells, works to prevent other tumor-fighting T-cells from entering the tumors of pancreatic cancer patients, turning a primary immune system defense mechanism “completely useless in pancreatic cancer,” researchers said.

Without interference from gamma delta T-cells, tumor-attacking T-cells like CD4 and CD8 should be able proliferate and go after pancreatic cancer cells, which they now do not.

The study, “γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation,” recently published in Cell,  was developed by researchers at the New York University (NYU) School of Medicine, and suggests that targeting gamma delta T-cells in pancreatic cancers may improve the work of immunotherapies in boosting tumor-fighting T-cells.

“Standard immunotherapy does not work in pancreatic cancer, which is especially deadly. Now we have more information to help us understand why,” George Miller, MD, head of the Immunology Program at Perlmutter, an associate professor in the Department of Cell Biology at NYU Langone, and study’s senior author, said in a press release. “The main anti-tumor defense mechanism is rendered completely useless in pancreatic cancer.”

Miller and his team focused on pancreatic ductal adenocarcinoma (PDA), a particularly deadly form of pancreatic cancer. Despite the overall increase in cancer survival rates with therapies developed in the last two decades, only about 8 percent of patients with pancreatic cancer survive five years after their diagnosis.

Because PDA tumors have a high number of gamma delta T-cells — they represent nearly 40 percent of all T-cells in these tumors — the researchers hypothesized that these cells could be promoting pancreatic cancer. But their results revealed that gamma delta T-cells alone do not promote tumor growth, rather, they prevent CD4 and CD8 T-cells from working inside these tumors.

These findings underscore, once more, how complex the immune system is and that not all immune cells play the same roles in different cancers. The same gamma delta cells that allow pancreatic cancer cells to grow — without being targeted by tumor-killing T-cells — also fight other types of cancers, including colon cancer, melanoma, and some kidney cancers.

But for pancreatic cancers, they may have important implications in the development of new therapies or prognostic markers. Reducing the numbers or impairing the work of gamma delta T-cell in these patients may improve the way other immunotherapies work.

In fact, the investigators observed that mice with pancreatic cancer that had fewer than normal gamma delta T-cells had better outcomes, surviving on average one year longer than treated mice with normal numbers of such cells.

It might be difficult to move these findings into human settings, however. As Miller noted, there currently are no known drugs or therapeutic agents that blocks the action of gamma delta T-cells in humans.