Changes in the immune system after pregnancy could help women to fight off breast cancer, suggest findings of an animal study led by Cold Spring Harbor Laboratory scientists.
Using a mouse model, the research team found that a type of immune cell called gamma delta natural killer T-like cells (NKTs) go up in number following pregnancy. This expansion was seen particularly in breast tissue in these animals compared with females who had not given birth.
NKT’s are an unusual type of immune cell in that they can participate in both the innate and adaptive immune response. “It is possible that NKTs expand in response to the re-setting of whole-body immunity post-partum, with the child-bearing event providing signals that alter antigens across all maternal tissues as well as expanding specific immune cell populations,” write the investigators in the journal Cell Reports.
Scientists have known for a while that pregnancy has a big impact on the immune system, as well as other cells around the body. It is also known that risks for breast cancer change as a result of pregnancy, but the impact of pregnancy on the cells in breast tissue was less clear.
Camila dos Santos, lead researcher and author of the study based at Cold Spring Harbor Laboratory, and colleagues investigated what changes occur in the breast tissue after pregnancy by comparing female mice that had given birth with those that had not.
After observing the dramatic increase in NKTs in mice that had given birth, they searched for a reason for this increase. They found that the breast epithelial cells, which surround the lactation ducts, make a protein called CD1d.
The connection was confirmed in a mouse model that did not produce CD1d. In these animals, there was no increase in NKT cells following pregnancy and the breast epithelial cells quickly became cancerous after birth.
The researchers also looked at levels of other immune cells such as leukocytes, which previous studies have suggested go up after pregnancy, but they did not observe similar increases in this study.
“Given that leukocytes have been implicated in the activation of NKTs it is possible that molecular alterations, rather than changes to cellular abundance or antigen presentation of leukocytes, could play a role in inducing or sustaining the population of NKTs in post-pregnancy mammary tissue,” write the researchers.
Dos Santos and colleagues now want to investigate whether this new knowledge could be used to develop therapies to block breast cancer. “Strategies could be developed to induce NKT expansion in the absence of a true pregnancy,” they suggest. Adding that “the characterization of specific, pregnancy-induced TCR rearrangements could be leveraged in CAR-NKT immunotherapy, for example, which could also efficiently target disease that has already developed.”
