Obesity may reduce a fat-cell process that helps kill breast cancer cells, offering a possible explanation for its link to the disease, a study found.

The findings come from preclinical models, including breast tissue from donors.

The research team at Huntsman Cancer Institute at the University of Utah focused on adipocytes, the fat cells that make up much of breast tissue.

Adipocytes are larger in obesity than in lean tissue and create different environments around cancer cells.

Researchers found that lean adipocytes produced much more of a fatty acid called 9S-HODE than obese adipocytes.

9S-HODE promotes ferroptosis, a form of cell death that helps the body remove old and damaged cells, including cells that could be cancerous.

Cancerous cells died more readily in lean tissue, where levels of 9S-HODE were higher.

Meghan Curtin, first author and a doctoral candidate in molecular biology, said: “We found that the lean adipocytes produce much more 9S-HODE than obese ones. This means that cancerous cells die more readily in lean tissue.

“By producing more 9S-HODE, our bodies are actively protecting us, under lean circumstances, in a way it cannot with obesity.”

In preclinical mouse models, increasing levels of 9S-HODE in obese adipocytes suppressed breast cancer tumour growth.

The researchers believe this understanding could lead to better therapies.

Keren Hilgendorf, senior author of the study and an investigator at Huntsman Cancer Institute, said: “From a clinical perspective, this discovery is incredibly empowering. Because 9S-HODE is naturally present in the body but is lost with obesity, we may be able to restore this protection by putting it back.”

“That could become a very feasible therapeutic approach to slow breast cancer growth.

The researchers stressed that obesity is only one factor that contributes to breast cancer and that the disease can develop for other reasons.

They also said 9S-HODE appears to be produced mainly by fat cells in the breast, although fat cells elsewhere in the body may have a similar protective function that requires further research.

Targeting CD1d altered immune cells slowed tumour growth and improved immunotherapy responses in mouse models of breast cancer, researchers found.

The findings suggest blocking the molecule could make the environment around breast tumours more favourable to anti-cancer immune responses.

Further work is needed to understand how these immune changes occur and how the approach could be safely used in patients.

Researchers from King’s College London, the Francis Crick Institute and University College London investigated how immune cells inside breast tumours influence cancer growth.

They focused on myeloid cells, a group of immune cells found in large numbers within tumours that can either support an immune attack against cancer or contribute to tumour growth and immune evasion.

The team examined CD1d, a molecule found on the surface of myeloid and other immune and tissue cells that helps regulate immune responses.

When CD1d was genetically removed from cells in a mouse model of breast cancer, the mice were more resistant to tumour growth. Researchers also saw changes in myeloid cell populations, including increased activity among cells that can help attack cancer.

The team then blocked CD1d using an antibody and again observed changes in myeloid cells and slower tumour growth. Blocking CD1d also improved responses to immunotherapy in the mouse model.

Researchers used single-cell RNA sequencing, a technique that examines gene activity in individual cells, to investigate the immune changes in more detail.

They identified a population of myeloid cells called monocytes that expressed genes associated with inflammation, an important part of the immune response. These cells were particularly important in restricting tumour growth in the mouse models.

A similar pattern of gene activity was identified in data from human breast cancer tumours. Its presence in myeloid cells was associated with positive responses to immunotherapy in breast cancer patients.

However, the findings in people were based on gene expression data and did not test CD1d-targeting treatment in patients.

Professor Patricia Barral, professor of immunobiology at King’s College London and senior author of the study, said: “Many breast cancers do not respond well to current immunotherapies.

“Our findings reveal a previously unrecognised mechanism by which immune cells within tumours are regulated.

“While CD1d is best known for helping immune cells recognise lipid molecules, we found that it also plays a role in shaping the behaviour of myeloid cells within tumours.

“These findings suggest that targeting the immune cells that surround and support tumours could boost anti-cancer immunity and potentially improve treatment responses in the future.”

Researchers now plan to investigate how the immune changes occur and how they can be safely harnessed in patients.

They also want to examine whether targeting CD1d could enhance existing treatments and influence treatment responses in different cancer types.

The work was supported by UKRI BBSRC, Breast Cancer Now and the Cancer Research UK City of London Centre.

An experimental cancer drug reduced bone loss and body fat in mice modelling post-menopausal changes, early research suggests.

The compound, CADD522, appeared to strengthen bones and help the animals stay leaner after surgery designed to mimic hormonal changes seen after menopause.

The treatment remains at an early experimental stage and has so far only been tested in animals.

The study, led by the University of East Anglia, investigated CADD522, which was originally developed to block a protein involved in the growth and spread of several cancers.

Mice treated with the compound for eight weeks showed significant improvements in bone health. Scans found increased bone volume and better preservation of the honeycomb-like structures inside bones that are crucial for strength and resilience.

Blood tests suggested the treatment stimulated new bone growth without interfering with the body’s normal process of breaking down and rebuilding bone.

Dr Darrell Green, lead researcher from UEA’s Norwich Medical School, said: “Osteoporosis affects around one in three women over the age of 50, leaving sufferers vulnerable to painful fractures that can seriously impact quality of life.

“Current treatments exist, but many are plagued by side effects, safety concerns or inconvenient dosing schedules that make long-term use difficult.”

The researchers also found that mice receiving CADD522 weighed less than untreated mice despite eating the same amount of food.

They had less body fat and fewer fat deposits in their bone marrow, a process commonly seen after menopause and linked to declining bone health.

The team also examined brain tissue and found that the drug appeared to reverse several menopause-related changes in fatty acids.

Levels of omega-3 fats including DHA remained largely intact, while several other lipid abnormalities shifted back towards healthier patterns.

Green said: “We didn’t directly test for memory or thinking ability, but our work raises questions about whether this drug could one day help address wider menopause-related health problems.”

Safety experiments in mice, rats and dogs found that CADD522 could be taken orally and was well tolerated.

The compound also appeared to be metabolised more slowly in human tissue than in rodents, potentially improving its performance in people.

“This is still in the early stages and has so far only been tested in animals but we hope that the benefits will translate to humans to ultimately reduce fracture rates,” added Green.

The research was led by UEA in collaboration with the University of Maryland, the Scintillon Research Institute in San Diego and the University of Stirling.

Safety testing was funded by The Sir William Coxen Trust as part of the development of CADD522 as a childhood cancer treatment.