According to the American Cancer Society, more than 20,000 women are diagnosed with ovarian cancer every year in the U.S. For most of these women, the cancer has already spread to other organs (metastasized) at the time of diagnosis.
In addition to malignant cancer cells, tumors are composed of a network of immune cells, blood vessels, chemical signals, and support structures. These other components are known as the “microenvironment.” Cold Spring Harbor Laboratory (CSHL) Professor Mikala Egeblad studies how the microenvironment helps tumors spread to other organs. In research supported in part by Swim Across America (SAA), the Egeblad lab is studying the role of recruited immune cells, such as macrophages and T cells, in ovarian cancer metastases. Macrophages normally kill and attack bacteria, but such beneficial functions can get corrupted by cancer cells, so they instead help cancer to spread.The Egeblad lab is working on identifying drugs and vaccine components that can “reprogram” macrophages in ovarian cancer to do beneficial jobs instead, such as using their ability to kill bacteria to kill cancer cells. MPLA (monophosphoryl lipid A) is a synthetic component from bacteria and is used in some vaccines to boost the immune system. In recent work published in the journal Cancer Cell, the Egeblad lab used MPLA in mice with metastasized ovarian cancer. When MPLA was given alone, it was not sufficient to treat the cancer. However, when combined with interferon-gamma, a signal molecule naturally used by immune cells to communicate with one another, the combination treatment reprogrammed macrophages to work together with killer T cells to attack the metastasized ovarian cancer cells. When the macrophage-reprogramming treatment was combined with chemotherapy, mice lived much longer than mice treated only with chemotherapy.
SAA is a national organization that funds cancer research, clinical trials, and patient programs by hosting annual charity swims. The SAA charity swims partner with beneficiaries in their local communities. Beneficiaries volunteer at the swims, share stories of impact, and join swims. Thousands of swimmers participate in more than 20 swims around the nation each year.
Egeblad explains her research program as follows: “We want to understand both the good and the bad side of the microenvironment. The funds from SAA are helping us understand how to change a bad microenvironment to a good one. We are also studying how cancers first ‘set up shop’ when they arrive at new organs. When metastatic cancers first arrive at a new location, that location isn’t set up to nourish them,” Egeblad says. “We’d like to understand how metastases develop, what enables cancer cells to succeed in the new organ, and why it is not eliminated or controlled by the immune system. This will be key to figuring out how to put an end to cancers’ spread.”