A new way in has been identified by Massachusetts General Hospital (MGH) investigators, in which a type of lung cancer co-opts a portion of the immune system to increase tumor progression. In the study published in the journal Science, the team from the MGH Center for Systems Biology describes a "crosstalk" between lung tumors and bone marrow, which leads to the generation of a type of immune cell that travels to the tumor and promotes its progression.
"Immune cells play critical roles in cancer. For example, we already know that T cells can eliminate tumors and be activated with immunotherapies. Tumors are home to diverse immune cell types, some of which remain much less explored than T cells and could also control cancer progression" says Mikael Pittet, PhD, director of the Cancer Immunology Program in the MGH Center for Systems Biology and senior author of the Science paper. "Myeloid cells are immune cells that are attracting attention because they can infiltrate a broad range of tumors. These cells include neutrophils and macrophages and seem to modulate key cancer-associated activities."
Recent research has suggested that tumor-infiltrating myeloid cells are initially produced in the bone marrow. For the current study the MGH team further explored whether bone marrow activity was altered in the presence of cancer in another part of the body, in this instance lung cancer. Their initial experiments found increased bone activity in two mouse models of a common form of lung cancer and in 70 lung cancer patients, even in absence of bone metastasis. Both the number and activity of osteoblasts - cells that produce and reshape bone tissue - were increased within the bone marrow of mice with lung tumors compared with cancer-free animals; and reducing the number of osteoblasts in mice not only limited neutrophil infiltration of tumors but also interrupted tumor progression.
"Our findings indicate the existence of long-distance interactions between lung tumors and bones: lung tumors remotely activate osteoblasts, and those bone cells, in turn, shape immunity by supplying tumors with cancer-promoting neutrophils," says Pittet, who is an associate professor of Radiology at Harvard Medical School. "Since patients with many types of cancer have elevated levels of myeloisd cells in their blood, it's possible that other tumors could have a similar interaction with bone to increase myeloid cell production."
Pittet adds that this study "shows the importance of studying cancer as a systemic disease.We have started to study the complexity of myeloid responses to cancer and to identify molecular and cellular components that promote the disease. With the ultimate goal of improving patients' quality of life, we hope that modulating myeloid pathways will overcome some of the limitations of current treatment options."