Breast cancer cells can reprogram immune cells for metastasis

Scientists from the Johns Hopkins Kimmel Cancer Center have uncovered a mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body. They propose that immunotherapy strategies targeting this process, described in the Journal of Cell Biology, could be developed to halt or prevent metastasis and reduce breast cancer deaths.

Natural killer (NK) cells, a type of immune cell, are known to limit metastasis by inducing the death of cancer cells. But metastases still form in patients, so there must be ways for cancer cells to escape. Using a novel cell culture method, developed by Johns Hopkins’ Dr Isaac Chan in the laboratory of Professor Andrew Ewald, the researchers studied the interactions between NK cells and invasive breast cancer cells in the laboratory in real time. They discovered that metastatic breast cancer cells can reprogram NK cells so that they stop killing cancer cells and, instead, assist in metastasis.

“Metastatic disease is the main driver of breast cancer deaths, and we need a deeper understanding of how and why it occurs,” said Dr Chan, who served as lead author on the study. “Our research has identified a new strategy for cancer cells to co-opt the immune system. If we could prevent or reverse natural killer cell reprogramming in patients, it could be a new way to stop metastasis and reduce breast cancer mortality.”

“Our study showed that NK cells selectively target the cells that initiate the metastatic process and also how the cancer cells trick the immune system into helping them,” added Prof Ewald, senior author on the study. “This study also highlights the power of multidisciplinary cancer research. This project brought together medical oncology, cell biology, immunology and biomedical engineering to understand metastasis.”

Using molecular profiling and computational analyses developed by Professor Joel Bader and Hildur Knútsdóttir, a fellow in Prof Bader’s lab, the researchers were able to map every suspected molecular interaction between immune cells and cancer cells — and identify the ones that were likely regulating this communication.

“As predicted, when we blocked these inhibitory signals, the NK cells continued to be the ‘good guys’ and kept clearing out cancer cells,” Prof Ewald said. “We’re excited this approach could be used to prevent metastases from forming, and we’re also testing whether this same approach could be used to reactivate an immune response to an existing metastasis.”

The investigators say the process may also apply to other cancer types. Immunotherapies that target NK cells could also potentially be used together with existing immunotherapies that stimulate T cells to fight cancer.

Image caption: A blue tumour organoid surrounded by red NK cells. Image credit: Isaac Chan, MD, PhD.

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