Although we commonly think of the immune system as protecting us, cancer researchers have found that sometimes an immune reaction may grow a tumor instead of killing it. Now, a new study conducted by researchers at the University of California, San Diego, has found evidence that the levels of circulating antibodies may influence tumors in radically different ways. “As always, it turns out that the immune system is a double-edged sword,” said Dr. Ajit Varki, distinguished professor of medicine and cellular and molecular medicine and principal investigator of the published research. Even more, Varki and his colleagues have verified some of the ways in which our immune response is linked to an acid injested when we eat meat and dairy products.

The Surface of Cells

In all organisms, the surfaces of all cells are embellished with a complex array of sugar chains known as glycans. Scientists have discovered these chains help to mediate or modulate various biological processes, including signalling, sub-cellular and cellular trafficking, intercellular adhesion, and microbial attachment. Sialic acids are found at the outermost position on the glycan chains of vertebrate cell surfaces. One of these acids, n-glycolyl-neuraminic acid or Neu5Gc, is not produced by the human body yet it has been found in human tumors. Neu5Gc is ingested when we eat red meat and dairy products, and then it binds to the glycan chain on cells. From there, scientists believe the body produces an inflammatory immune response to it as if it were a foreign antigen.

For the current study, Varki and his colleagues investigated Neu5Gc more closely. First, the scientists created a mouse model with a human-like tumor that had Neu5Gc adhering to the surface of its cells. Next, they deployed antibodies against the Neu5Gc in that model in order to understand whether and to what degree the antibodies altered tumor progression. They discovered that low antibody doses stimulated growth, but high doses inhibited it. What surprised them was the range of this diametric effect.

According to Varki, the outcome occurred over a "linear and remarkably narrow range." His team of scientists concluded that the difference in intensity between an immune response that stimulates tumors and one that kills them may be much less than previously imagined. "This may come as a surprise to researchers exploring two areas typically considered distinct: the role of the immune system in preventing and killing cancers and the role of chronic inflammation in stimulating cancers," Varki stated in a press release. The researchers found that immune response could be shifted rather easily, a finding they replicated in additional experiments with two other mouse tumor models and one grafted human tumor model.

Varki suggested these results may have implications for all aspects of cancer science and he, himself, has been inspired to become a co-founder of Sialix Inc., a small biotech that recently received a $1 million cash infusion and also opened a new office in Cambridge, Massachusetts to complement its scientific headquarters in San Diego. The company is developing two products based on knowledge of the effects of sialic acid. One product is an antibody that targets solid tumors including ovarian, breast and colon cancers; the second product is a nutritional supplement designed to tame the immune response to sialic acid. For those who do not plan to give up meat or dairy, the second product may be particularly welcome.

 

Source: Pearce OMT, Laubli H, Varki NM, et al. Inverse hormesis of cancer growth mediated by narrow ranges of tumor-directed antibodies. PNAS. 2014.