New study from the wistar institute, published in the journal Cancer Cell, reported that a variation in a person’s DNA sequence called molecular polymorphism could lead to a chain of events, dictating how a tumor will progress in certain types of cancer, such as a form of breast cancer as well as ovarian cancer.
The study indicated that the interaction between the helpful bacteria in human body and immune cells at places situated away from tumors influence systematic responses in the host that alter how these tumors are able to progress.
Many of human cells are programmed to recognize pathogen-associated molecular patterns. Over 23% of the general public carries mutations in a group of pathogen recognition receptors called Toll-like receptor (TLR) genes. To be the most abundant polymorphisms is TLR5, which makes the people who do carry it susceptible to illnesses such as Legionnaires disease, and urinary tract infections.
Whether does TLR5 signaling influence cancer?
As shown from the research, TLR5 signaling influences certain types of cancer in different ways and is dependent upon the ability of the tumor to respond to interleukin 6 (IL-6), a small protein that can have both pro-inflammatory and anti-inflammatory properties.
In individuals with functional TLR5 expression, commensal bacteria are able to stimulate IL-6 production, as well as greater mobilization of myeloid-derived suppressor cells (MDSCs) , to produce high amounts of galectin-1, a protein that suppresses antitumor immune activity and hastens tumor progression.
While the researchers showed that TLR5 signaling does not always mean that tumors will grow faster. TLR5-deficient mice with tumors that produce low levels of IL-6 have faster tumor progression. In this instance, IL-17, another interleukin closely associated with autoimmune diseases and inflammation, is consistently found in higher levels in TLR5-deficient mice that have tumors, but IL-17 only accelerates cancer when the tumors are unresponsive to IL-6.
For ovarian cancer, which is associated with high levels of IL-6, researchers found a significantly higher number of TLR5-deficient patients alive six years after their initial diagnosis compared with patients with TLR5, indicating a correlation between the absence of TLR5 and improved survival. For luminal breast cancer, which is associated with low levels of IL-6, the long-term survival prospects were worse for patients without TLR5.
Reference:
Microbially Driven TLR5-Dependent Signaling Governs Distal Malignant Progression through Tumor-Promoting Inflammation. Cancer Cell, 2014