Unlocking the immune dynamics of metastatic breast cancer

Cancer metastasis is a process in which cancer cells disseminate from the primary tumor, settle and grow at a site other than the primary tumor site. Cancer mortality primarily stems from metastatic recurrence, emphasizing the urgent need for developing effective metastasis-targeted immunotherapies. Metastatic breast cancer still accounts for a substantial portion of breast cancer-related deaths, with a median survival time of about 12 months after metastasis. Understanding the mechanisms of metastasis can enable the development of targeted therapies that may improve survival rates and reduce the burden of the disease. Prof. Ido Amit, in collaboration with Prof. Neta Erez of Tel Aviv University’s Faculty of Medicine, used his state-of-the-art single-cell technologies and a model of metastatic breast cancer to investigate decipher the cellular and molecular events that allow primary breast tumors to spread to the lungs. The team’s findings, published in the journal Cancer Discovery, demonstrate how the spread of breast cancer to the lungs is associated with specific changes in the balance of immune cell populations. As metastasis commences, the lungs experience heightened infiltration of immune cells known as macrophages. The these macrophages are hijaked by the tumor and activate diverse immune suppressive pathways commentating ind dramatic reduction in the anti-cancer activity of the immune system. The team also used advanced spitial technologies to map out where these cell-cell communications and found that a critical sub-population of these regulatory macrophages which activate a unique immune inhibitory signaling pathway (TREM2) is located at the invasive “boundaries” of cancer and shields the tumor from the body's immune defenses. These discoveries can contribute to improved immunotherapy protocols and the development of novel therapies that can save lives.