A new era of targeted treatments for metastatic cancer may be around the corner, an expert says, as new research shows some primary breast tumours stop their own spread by harnessing the body’s innate immune system.
Research published in Nature Cell Biology this week found that in both mice and humans, primary breast tumours elicited an inflammatory response through 1L-1β to freeze the growth of breakaway cancer cells in other parts of the body.
Among 215 patients with lymph node positive breast cancer, those with high 1L-1β expression in the primary tumour had improved overall survival relative to those with low 1L-1β expression, retrospective analysis showed.
The authors showed through a series of mouse models that the primary tumour was driving 1L-1β expression to lock secondary cells into a state where they could not proliferate.
For instance, mice with a primary tumour were less likely to develop macrometastases when injected with metastasis-inducing cancer cells from that same tumour, compared with mice lacking the primary tumour. Furthermore, when the 1L-1β inflammatory response was blocked – either at the primary tumour or metastatic sites – metastatic colonisation occurred.
A new era
Study co-senior author, Dr Christine Chaffer from the Garvan Institute of Medical Research said the findings constituted “a great advance, and one that suggests a novel way to combat metastases.”
“We think this immune system activation by the primary tumour is an unintentional by-product of the metastatic process, and one that we can hopefully enhance to fight cancer.”
“There has been so little progress until now in understanding the biological processes driving metastases,” she said. “This new discovery – combined with new single-cell sequencing technology which is able to tease out the composition of individual tumours and potentially identify aggressive tumour cell sub-populations – will hopefully yield a new era of targeted therapies for metastatic patients in the next 5-10 years.”
Dr Chaffer said she was optimistic the findings would bring hope to future patients with triple negative breast cancer – a disease which accounts for 25% of breast cancer cases but has an exceptionally poor prognosis. Some 60% of patients experience recurrence that is metastatic and/or chemo-resistant.
‘Innate’ not ‘adaptive’ immunity
Melanoma research has had the lion’s share of cancer breakthroughs in the last decade, especially with the advent of immunotherapy. However Dr Chaffer noted that such immunotherapy had not been shown to work well in breast cancer.
“It’s now apparent that the adaptive immune response plays a major role in melanoma, whereas this is not necessarily the case in breast cancer. Our research shows the important role of the innate immune system in suppressing breast cancer,” she said.