Exciting new studies investigating a new type of therapy called immunotherapy are underway for patients with breast cancer. Immunotherapy works by re-training the body’s immune system to fight cancer. This type of therapy holds great promise to prevent cancer from coming back and to help patient’s live longer and enjoy better quality of life after fighting cancer. When people get sick with breast cancer, the body’s immune system works to recognize the cancer cells and tries to eliminate them. However, the tumor cells send signals to turn the immune system off and then the immune cells cannot do their job to recognize the tumor cells as ‘foreign’. This allows the tumors to grow and eventually spread and kill people. We are working toward discovering what immune cell types, are able to get inside of tumors and how they work to prevent the appropriate immune response, this is called immunosuppression. Once we identify these immunosuppressive signals we can design therapies that will reverse these signals and improve elimination of tumor cells using the body’s natural defenses.
By combining new types of treatment that eliminate the immunosuppressive signals with traditional immunotherapy, we hope to improve response rates in patients. We will also determine if the other cells that make up tumors are different when they are found inside tumors in the breast versus when they are found in tumors that have moved outside the breast (i.e. in metastatic disease).
We collaborate with other labs internationally to achieve these goals. One example of new technologies that we use is called single cell RNA sequencing, which decodes the gene expression profiles of each individual cell in a tumor sample, giving us a near-complete picture of all the different cells present and their characteristics. We can use this technology to evaluate thousands of genes in tens of thousands of cells and track each cell following different types of experimental treatments. An example of one of our most recent discoveries using this technology, is that one of the immune cells called macrophages, change their identity when the move into tumors and promote tumor growth. We found a target on these macrophages that can be blocked using new drugs that change the macrophages back to supporting the immune response and eliminating tumor cells instead of supporting their growth. We are currently performing experiments to test this drug in the lab and hope to bring this to patients in the form of phase I-II clinical trials soon.
This type of technology as well as other cutting edge experiments will help us determine with great precision the developmental origin, susceptibility to treatment and overall functional role of different immune cells within tumors and metastatic sites. Overall, these discoveries could revolutionize how we treat patients with breast cancer and help people live longer and happier lives.
A long term goal of immunotherapy is to significantly prolong the lives of patients with breast cancer without the toxicity of traditional chemotherapy. Unlike chemotherapy, the beneficial effects of immunotherapy continue to work even after treatment has stopped. These lasting effects translate to years of improved quality of life and disease stability even in cases where breast cancer has spread to other organs in the body. One hurdle that needs to be overcome is to broaden the approval of immunotherapy to include more patients diagnosed with breast cancer.
To help bring this life saving therapy to more patients, we need to determine how to improve its effects. In the short term, my work will contribute to understanding how to improve the beneficial effects of immunotherapy by combining it with low dose chemotherapy. There are studies that suggest this combination may even be more beneficial in recruitment of the immune system than when given with full doses of chemotherapy. The other benefit of this approach would be that it is less toxic and prolongs disease free survival. I have designed experiments that will investigate what dose of chemotherapy will work to maximize the benefit of the body’s own immune system and minimize toxicity.
Our work also aims to learn about the differences in the immune response when a patient’s cancer is confined to the breast versus when it has spread throughout the body. These findings will help make immunotherapy part of the standard of care for patients with breast cancer.