Blocking IL1b with anakinra controls tumor-promoting inflammation in breast cancer
A cytokine signature found in certain kinds of breast cancer cells can not only serve as a diagnostic tool for HER2-negative cancers but also offer an effective treatment target.
Human breast cancer tissue stained by immunofluorescence illustrates the interplay between secreted and surface-bound TGFβ (red) expressed by cancer cells (blue), which primes tumor-infiltrating myeloid cells to produce IL1β (green). This in turn will lead to chronic inflammation associated with breast cancer progression. Gray, nuclei.
Credit: Jackson Laboratory
A research team led by Karolina Palucka, M.D., Ph.D., a professor at The Jackson Laboratory (JAX), has collaborated with researchers at The Baylor Institute for Immunology Research to show that IL1b, a member of the interleukin 1 family of cytokines (proteins released by certain cells of the immune system) drives the inflammation often found in cancer, and appears as an "IL1 signature" in women with HER2-negative metastatic breast cancer.
"We found that IL1b orchestrates tumor-promoting inflammation in breast cancer," Palucka says, "and its presence corresponds with poor clinical outcomes. We show that it can be effectively targeted in patients using anakinra, a naturally occurring IL1 receptor antagonist."
Anakinra is already widely used to treat autoimmune and autoinflammatory diseases, and is being tested as an adjunct therapy to reduce the inflammation of metastatic cancer, including metastatic colorectal cancer.
In the new study, 11 women with advanced metastatic HER2-negative breast cancer received anakinra treatment, and after just two weeks showed reduced gene expression of IL1b and other cytokines and signaling pathways.
The patients then received anakinra in combination with standard chemotherapeutics for HER2-negative cancers for a median duration of four months. Some patients reported less pain and increased quality of life during this combination treatment, and three of them are still alive.
The team's report appears as the cover article in the journal Cancer Research, along with a commentary by Charles A. Dinarello, Ph.D., of the University of Colorado Denver Anschutz Medical Campus, who discovered, cloned and characterized the essential biology of a human "fever molecule," which was later named Interleukin-1 (IL-1).
"The study represents several years of dedicated research on cancer by Palucka and colleagues," Dinarello writes. "Although there are several advantages of knowing a transcriptional signature, including risk and prognosis, a real benefit is the exploitation of the signature to develop specific, targeted therapies. In the case of patients with cancer with IL-1 signature genes, one could simply block IL1. In fact, this is exactly what the study accomplished."
email@example.com | EurekAlert!
Photoactive bacteria bait may help in fight against MRSA infections
12.10.2018 | Purdue University
15 emerging technologies that could reduce global catastrophic biological risks
10.10.2018 | Johns Hopkins Center for Health Security
Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles
Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...
When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.
We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...
Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...
Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...
New measurement method allows researchers to precisely follow the movement of individual molecules over long periods of time
The function of proteins – the molecular tools of the cell – is governed by the interplay of their structure and dynamics. Advances in electron microscopy have...
16.10.2018 | Event News
02.10.2018 | Event News
01.10.2018 | Event News
16.10.2018 | Life Sciences
16.10.2018 | Physics and Astronomy
16.10.2018 | Event News