'Thin red line' around breast cancer

May 2, 2012
This is a confocal microscope image of a spontaneous breast cancer tumor in a mouse. Credit: UCSF

A pioneering approach to imaging breast cancer in mice has revealed new clues about why the human immune system often fails to attack tumors and keep cancer in check. This observation, by scientists at the University of California, San Francisco (UCSF), may help to reveal new approaches to cancer immunotherapy.

Published in the journal Cancer Cell last month, the work shows that the body's natural defenses trip over themselves on their way to attacking a tumor. The activated immune cells, alerted to the threat of the tumor, should make their way to the site of the cancer and then attack and shrink the tumor.

Instead, these immune cells are headed off at the pass. A completely separate set of healthy cells that are already in contact with the tumor effectively establish a defensive perimeter around it. There, like a thin red line between cancer and health, they head off the killer immune cells and keep them at bay outside the tumor.

"These cells are forming a last line of defense for the tumor against incoming cytotoxic cells," said Matthew Krummel, PhD, an associate professor of pathology and a principal investigator in the UCSF Helen Diller Family Comprehensive Cancer Center.

The discovery adds a rich layer of understanding of how the interacts with breast cancer, knowledge that may ultimately help researchers find better ways to treat the disease, said Krummel. Future immunotherapy cancer treatments could be made more effective on their own or in combination with other drugs, he said, if researchers can find a way to enhance the ability of T cells to make it through this tumor defense.

Unlocking the Secrets of Cancer

Cracking open a crashed airplane's black box to parse its flight data and recreate its final few seconds is a powerful way of asking how improvements could be made to aviation safety. Biologists would like to do essentially the same thing with cancer: to liberate the data, see what went wrong and use that knowledge to find new ways to improve human health.

Because biology has no flight recorders, modern researchers look broadly at the genetics of large populations, or tease apart the molecular markers within tumors or closely following the disease as it develops in laboratory models.

Krummel and his colleagues developed a way to produce different fluorescent-colored dyes in breast cancer tumors and the various cells around them, They then used a special microscope to image and track immune cells as they moved in and out of breast cancer tumors that arise spontaneously in the mouse. "We can see each of them arise, see where they are in the tumor and watch their direct interaction with in real time," he said.

What they found was that the interaction between and the immune system is marked by missed opportunities.

Fighting cancer is one of the things the immune system is designed to do, in numerous ways. One of these is by unleashing a set of actors known as killer T cells, which can destroy tumors by attacking their cells en mass. The success of this mechanism can mean the difference between a tumor that withers away and one that continues to grow to more advanced stages.

But the scene Krummel and his colleagues watched unfold under their microscopes revealed a subset of specialized "dendritic" cells that they were then able to extensively study. With the fluoroscent labeling technique they devised, they were able to purify just these cells and observe how they dampen the killer T cell responses.

As Krummel and his colleagues showed, these cells deactivated approaching killer cells, stifling them before they could spring into action.

This set of experiments is critical for cancer immunobiologists, said Krummel, because the data is the first to positively identify a partner for the incoming killer . The fact that the interaction dampens the potency of the killer cells makes the dendritic cells a valuable target for future therapeutics.

Explore further: Enhancing the effectiveness of a breast cancer treatment

Related Stories

Enhancing the effectiveness of a breast cancer treatment

February 13, 2012
Breast cancers expressing the protein HER2 have a particularly poor prognosis. Treatment with trastuzumab (Herceptin) benefits some patients with HER2-positive breast cancer, but it is not as effective as had been hoped. ...

How to rescue the immune system: Study could lead to novel therapy for cancer

February 26, 2012
In a study published in Nature Medicine, Loyola researchers report on a promising new technique that potentially could turn immune system killer T cells into more effective weapons against infections and possibly cancer.

Stem cells, potential source of cancer-fighting T cells

September 20, 2011
Adult stem cells from mice converted to antigen-specific T cells -- the immune cells that fight cancer tumor cells -- show promise in cancer immunotherapy and may lead to a simpler, more efficient way to use the body's immune ...

Recommended for you

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

Searching for the 'signature' causes of BRCAness in breast cancer

August 21, 2017
Breast cancer cells with defects in the DNA damage repair-genes BRCA1 and BRCA2 have a mutational signature (a pattern of base swaps—e.g., Ts for Gs, Cs for As—throughout a genome) known in cancer genomics as "Signature ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.