Novel compound that engages 'second arm' of immune system reduces breast tumors and metastases

March 8, 2017
Dr. Guerriero led a new study that shows a compound able to reverse the allegiance of innate immune system cells -- turning them from tumor enablers into tumor opponents -- caused breast tumors in mice to shrink and withdraw from distant metastases. Credit: Dana-Farber Cancer Institute

For all the success of a new generation of immunotherapies for cancer, they often leave an entire branch of the immune system's disease-fighting forces untapped. Such therapies act on the adaptive immune system, the ranks of specialized cells that mount precision attacks on foreign and diseased cells. The other arm of the immune system, known as innate immunity, may not be merely idle during this battle, but may actually abet tumor growth.

In a new study in the journal Nature, Dana-Farber Cancer Institute scientists report that a compound able to reverse the allegiance of innate immune system cells - turning them from tumor enablers into tumor opponents - caused in mice to shrink and withdraw from distant metastases. When combined with chemotherapy or another immunotherapy, the new compound significantly extended the period of tumor remission.

The findings suggest a way to bring the full repertoire of the immune system to bear on cancer in humans, the authors said.

"Most current forms of cancer immunotherapy influence the behavior of T cells - that are part of the adaptive immune system - by 'teaching' them to attack or removing impediments to such an attack," said the study's lead author Jennifer Guerriero, PhD, of Dana-Farber. "This strategy has been effective against several types of cancer, but generally only a subset of patients benefit. We wanted to see if harnessing both arms of the immune system could produce superior results."

The targets of the new study were innate known as tumor-associated macrophages (TAMs). They're often found deeply embedded within tumors, but although they're part of the immune system - the body's defense against disease - they frequently promote . In doing so, they're responding to cues issued by the tumor itself.

The roles that macrophages play - whether protective or destructive - depend on signals from their environment. In wound healing, for example, macrophages marshal the elements of the immune system that clear away damaged tissue and restore the affected area. Tumor macrophages manage to hijack some of these supportive functions for their own purposes. Not without reason is cancer sometimes referred to as a wound that doesn't heal.

In previous research, the Dana-Farber scientists and their colleagues showed that a compound known as TMP195 could convert TAMs from aiding tumor growth to organizing an attack on it. A selective, first-in-class, class IIa HDAC inhibitor, TMP195 switches the macrophage response by altering gene activity within TAMs.

In this current study, TMP195 sharply reduced the rate of tumor growth in mice with breast tumors, researchers found. They next combined TMP195 with various chemotherapy regimens and with a form of immunotherapy known as T-cell checkpoint blockade. In both cases, the combinations produced longer-lasting remissions of breast cancer than TMP195 alone did.

"Once they've undergone conversion, macrophages act as the orchestrators of the immune system attack on the tumor," said Anthony Letai, MD, PhD, of Dana-Farber, co-senior author of the study with Michael A. Nolan, PhD, of GlaxoSmithKline. "Our findings demonstrate that class IIa HDAC inhibitors can be an effective way of harnessing the anti- potential of macrophages in cancer therapy.

"The future of cancer treatment is likely to involve combinations of therapies that act on both the innate and adaptive arms of the immune system, as well as therapies, such as chemotherapy, radiation therapy, or targeted therapy, that act on cancer cells themselves," he continued. "The ability to engage the innate is an exciting new front in therapy."

Explore further: Scientists stimulate immune system, stop cancer growth

More information: Jennifer L. Guerriero et al. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages, Nature (2017). DOI: 10.1038/nature21409

Related Stories

Scientists stimulate immune system, stop cancer growth

March 1, 2017
A chemical found in tumors may help stop tumor growth, according to a new study.

Newfound effect of cancer drug may expand its use

February 10, 2017
A drug first designed to prevent cancer cells from multiplying has a second effect: it switches immune cells that turn down the body's attack on tumors back into the kind that amplify it. This is the finding of a study led ...

Fighting cancer with the power of immunity

October 24, 2016
Harnessing the body's own immune system to destroy tumors is a tantalizing prospect that has yet to realize its full potential. However, a new advance from MIT may bring this strategy, known as cancer immunotherapy, closer ...

Uncovering the mechanisms that support the spread of ovarian cancer

October 10, 2016
A very high mortality rate is associated with ovarian cancer, in part due to difficulties in detecting and diagnosing the disease at early stages before tumors have spread, or metastasized, to other locations in the body.

Innate immunity may help limit cancer growth

September 17, 2015
Cancer immunotherapy, a relatively new frontier in cancer treatment, works by enhancing the capacity of one's immune system to attack cancer cells. To date, this field has focused on developing cancer vaccines or engineering ...

Recommended for you

Bolstering fat cells offers potential new leukemia treatment

October 16, 2017
Killing cancer cells indirectly by powering up fat cells in the bone marrow could help acute myeloid leukemia patients, according to a new study from McMaster University.

Study reveals complex biology, gender differences, in kidney cancer

October 13, 2017
A new study is believed to be the first to describe the unique role of androgens in kidney cancer, and it suggests that a new approach to treatment, targeting the androgen receptor (AR), is worth further investigation.

Cholesterol byproduct hijacks immune cells, lets breast cancer spread

October 12, 2017
High cholesterol levels have been associated with breast cancer spreading to other sites in the body, but doctors and researchers don't know the cause for the link. A new study by University of Illinois researchers found ...

New drug hope for rare bone cancer patients

October 12, 2017
Patients with a rare bone cancer of the skull and spine - chordoma - could be helped by existing drugs, suggest scientists from the Wellcome Trust Sanger Institute, University College London Cancer Institute and the Royal ...

Scientists pinpoint surprising origin of melanoma

October 12, 2017
Led by Jean-Christophe Marine (VIB-KU Leuven), a team of researchers has tracked down the cellular origin of cutaneous melanoma, the deadliest form of skin cancer. The team was surprised to observe that these very aggressive ...

Team finds a potentially better way to treat liver cancer

October 12, 2017
A Keck School of Medicine of USC research team has identified how cancer stem cells survive. This finding may one day lead to new therapies for liver cancer, one of the few cancers in the United States with an incidence rate ...

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.