For years researchers have been quite confused as to the contrary correlation between immunological responses and the spread of cancers. Though a strong immune system is often an indicator of a healthy attack against disease, in some forms of cancer it can also indicate civil war that will undoubtedly aid the cancer in the course of its infection. In particular, researchers investigating lethal forms of breast cancer have found shockingly active immune systems causing metastases of the cancer to other regions of the body, and now they think that they understand why.
In a new study published today in the journal Nature, researchers with the Netherlands Cancer Institute led by Dr. Karin de Visser say that in many lethal cases of breast cancer, the primary factor playing into the cancer's spread may be the host's very own immune system. Prior research indicated that increased presence of neutrophils active in the blood could put patients at a higher risk of developing metastases, however, until now researchers were unable to understand why. By investigating neutrophils and their cascade effects within immunological pathways, the team was able to reveal that while neutrophils may protect the body in most diseases, when it comes to breast cancer they decide to switch sides and act our against other members of the immune system.
Activated by signaling molecules released by malignant tumors, what would ordinarily become a normal inflammatory reaction turns awry when neutrophils are recruited by the cancer. Instead of protecting the host, these neutrophils instead protect the cancer by inhibiting and blocking the action of adaptive immune cells called "T Cells".
The signaling protein investigated by the researchers, which was revealed to have a significant role in neutrophil production and modification was Interleukin 17 (IL17). In mouse models the researchers were ale to inhibit IL17 pathways, and found that indeed the signaling protein was not only essential in producing greater numbers of neutrophils, but also in helping them change to T Cell inhibitors.
"We saw in our experiments that IL17 is crucial for the increased production of neutrophils", de Visser says. "And not only that, it turns out that this is also the molecule that changes the behavior of the neutrophils, causing them to become T cell inhibitory."
"What's notable is that blocking the IL17-neutrophil route prevented the development of metastases, but did not affect the primary tumor. So this could be a promising strategy to prevent the tumor from spreading."
While in western nations the development of breast cancer amongst women is roughly one in eight, of those that die 90 percent succumb to cancer because the tumors metastasize and spread throughout the body. For this reason, de Visser and her team of researchers believe that understanding the culprit and the signaling pathways that causes them to act in defiance, is vital in combatting metastases and breast cancer in the near future. Now, with a better understanding of neutrophils and the role of IL17, the team hopes to be able to counter metastases and better the odds of beating breast cancer altogether.
