Chair of the Department of Cell, Developmental and Cancer Biology of the Knight Cancer Institute at the Oregon Health and Sciences University Lisa Coussens spoke at the University of Wisconsin on Wednesday about her research on the relationship between inflammation and cancer. The seminar was a part of the weekly Cancer Biology Seminar Series hosted by the McArdle Laboratory for Cancer Research.
Coussens started the seminar with the history of scientists’ understanding of the interplay of the immune system and cancer. She reviewed her previous work on pre-cancerous tissues and her thought process after finding immune cells consistently involved in the tissues. Coussens recalled her colleagues and immunologists who believed the immune system was failing to prevent cancers from developing. But, Coussens thought differently.
“Mother Nature’s conservative, it wouldn’t mount the significant immune infiltrates if they weren’t playing a fundamental role in, perhaps, facilitating cancer development,” Coussens said.
Digging deeper, Coussens found that the types of immune cells that infiltrated into pre-cancerous cells resembled the makeup of healthy tissues more than they resembled the makeup in other pre-cancerous sites. The similarity helped further Coussens’ research that the immune infiltration was a normal process, but possibly interlinked with the development of cancer.
Coussens said the ability to use mice models to research cancer development allowed for a holistic understanding of the role the immune systems play. Researchers stumbled upon a mouse that naturally did not have macrophages, a white blood cell that engulfs and destroys pathogens and cancer cells. Comparing the progression of breast cancer in normal mice to ones missing macrophages, researchers found the ones without macrophages had less severe tumors that metastasized less often.
Coussens next step was to identify how the macrophages helped breast cancer cells. Several proteins secreted by macrophages promoted tumor development and metastasis. The pathways to creating the proteins were promoted both by the tumor and CD4 T helper cells. Helper T cells signal to other cells in the immune system to mount an immune response, including macrophages and killer T cells.
Spotting an opportunity, Coussens explored if preventing tumors from signaling to macrophages would slow tumor progression. Using pexidartinib, they targeted the CSF-1 receptors on macrophages. CSF-1 causes precursor cells of macrophages to differentiate into macrophages and other immune cells. Pairing chemotherapy with pexidartinib, Coussens saw a reduction of tumor growth compared with untreated and single-drug treatments.
When taken to human trials, researchers found a systemic response to breast cancer that increased the number of killer T cells seeking cancer cells, memory cells programmed to mount a response to cancer cells, and PD-1 receptors and PD-L1 proteins telling cancer cells to self-destruct.
Coussens wants not only to help slow down tumor growth but also to see therapies reach “tumor control” where a tumor stops growing entirely.
“The goal has to be control, it has to be to put the tumor completely into regression or put those tumor cells into [arrest],” Coussens said.