J Cell Biol: Breast cancer cells turn immune cells into deadly allies.

July 18, 2020 /PRNewswire/ -- Breast cancer cells can alter the function of an immune cell called natural killer cells (NK) so that they do not kill cancer cells, but promote their spread to other parts of the body, researchers at The Johns Hopkins University School of Medicine have foundThe study, published recently in Journal of Cell Biology (JCB), suggests that blocking this reprogramming may prevent breast cancer from transferring to other tissues, which is the leading cause of death in breast cancer patientsBreast cancer cells spread to other parts of the body by invading the surrounding healthy breast tissue and into the circulatory system, which takes them to other tissues, where they form new metastatic tumors that spread to other parts of the bodyNK cells are white blood cells that identify and kill cancer cells that spread throughout the body"Breast cancer cells must overcome THE monitoring of NK cells to form distant metastasis," said Andrew Ewald, a professor of cell biology at Johns Hopkins University School of Medicine and associate director of the Cancer Invasion and Metastasis Program at the Sidney Kimmel Comprehensive Cancer Center"However, we don't fully understand how breast cancer cells escape NK cell-mediated immune surveillance in the early stages of circulation and transplantation to distant organsPhoto Source: Chan et al., 2020 Ewald and his colleagues found that while metastatic breast cancer cells are initially vulnerable to NK cells, NK cells can quickly change the behavior of potential killers and reprogram to promote late metastasisBy using several new methods to simulate metastasis in laboratory and mouse experiments, the researchers found that after encountering tumor cells, human and mouse NK cells lost the ability to limit tumor attack, instead helping cancer cells form new tumorsNK cells change dramatically when exposed to tumors, and thousands of genes are turned on or off to express different receptor proteins on the cell surfaceEwald and his colleagues found that TIGIT and KLRG1, antibodies to two key receptor proteins on the surface of NK cells, could prevent NK cells from helping breast cancer cells grow new tumorsFDA-approved drugs decitabine and azacitidine have similar effects, possibly because they block large-scale changes in gene activity by inhibiting DNA methyl transferaseThe researchers found that combining decitabine or azacitidine with anti-TIGIT and KLRG1 antibodies was particularly effective in preventing NK cells from enhancing the metastasis potential of breast cancer cellsThese results suggest that the synergy between DNA methyl metase inhibitors and receptor blocking antibodies suggests a viable clinical strategy to reactivate tumor-exposed NK cells to target and eliminate breast cancer metastasisEwald notes, "Combined with our observations, a large number of NK cells are early responders, and our data provide a preclinical basis for the concept of NK cell-oriented immunotherapy in patients with high risk of metastatic recurrence." "() References: Breast cancer cells talk s turn et al., cancer cells educate seicer cells to a metastasis-promoting cell state2020JCell Biol https://doi.org/10.1083/jcb.202001134.