The immune system can seem fickle and is easily influenced by more than just viruses and bacteria. It can be swayed by what we eat and affected by surprising sources including psychosocial factors. At the American Association for Cancer Research‘s Frontiers in Cancer Prevention Research meeting, scientists are taking a closer look at the link between increasingly common lifestyle factors, the immune system and cancer, with the ultimate goals of preventing and better understanding cancer development.
In one presentation to the meeting it was reported that obese mice experience a far lower immune response than do normal weight mice to a vaccine typically given to cancer patients, as found in studies by National Cancer Institute immunologists.
The diminished immune activity not only may explain the connection between obesity and heightened cancer risk, it also suggests that obesity might reduce the effectiveness of common vaccines, such as flu and tetanus.
According to Connie Rogers, Ph.D., MPH, a research fellow at the Laboratory of Tumor Immunology and Biology at the National Cancer Institute (NCI) in Bethesda, several studies over the years have implicated obesity with diminishing immune function. In the early 1990s, studies showed low antibody levels after vaccination in those who had a high Body Mass Index, or BMI, which is a measure of body fatness.
"We hypothesized that perhaps there are global immune impairments that occur in the face of obesity, and in turn, maybe this is one of several mechanisms that might lead to, or mediate, the relationship between obesity and tumor risk," she said.
Rogers and co-workers at NCI and at the University of Texas compared the immune system function of lean, overweight and obese mice. They created lean mice by slightly restricting their diets and watching carbohydrates. Mice that were given unlimited access to food with a mildly fat content, about 10 percent versus the usual 5 percent to 7 percent fat in their diet, became overweight. Mice that were given unlimited access to a diet made up of about 60 percent in fat, similar to consuming a diet plentiful in fast-foods, became overweight to obese.
"The mice differed in body fat," Rogers noted, "and we wanted to tease out whether it was the weight or body fat that impaired immune function, and if there was a fat threshold in regard to immune function."
The researchers injected mice with a vaccine usually used for cancer patients and which targeted tumor antigens commonly seen in breast, prostate or colon cancers. By stimulating the immune system and measuring a specific response, they could compare the extent of obesity-induced immune function impairment in each animal body type.
"We needed to simulate the immune system and be able to measure a specific response," she said. The study also served "as a tool to probe the immune system and to shed some light on whether obesity might be impacting patients we see who come in for cancer vaccine treatment."
The scientists gave mice a primary vaccination and two booster vaccines to mimic as closely as possible the schedule used in patients. They examined both the broad-based or innate immune responses, and the adaptive immune responses, including T- and B-cell responses to vaccination. While adaptive immune responses require prior exposure to a foreign protein such as a virus or bacterium, innate immunity does not.
"Interestingly, it looks like both innate immune responses such as natural killer cell function and T-cell proliferation to broad-based stimuli were impaired, and importantly, their adaptive immune responses to the vaccine were impaired," Rogers said. The group found that the obese mice failed to develop appropriate antibody levels and "their ability to proliferate in response to the vaccine antigens was impaired." Both are important for generating an adequate immune response to a vaccine.
Neither the lean mice nor the moderately overweight mice showed similar immune system impairments in response to vaccination, suggesting that the response might be a "stepwise decrease" in adaptive immunity, Rogers said.
"I think we now know that this obesity-induced impairment is fairly widespread, and affects many components of the immune system," she said. "The clinical and public health importance of this is that there are probably some significant long-term consequences. We targeted many components of the immune system, and several, such as general response to infection and tumor response to vaccine, for example, could be affected by this obesity-induced impairment in immunity."
"In the long term, we’re considering the usual cancer patient who is in his sixties and probably overweight," Rogers said. "But a basic biological question and one with public health significance is that of general immune health of overweight or obese people. That has an impact on long-term health."
Rogers and her team have several questions to explore. "Now that we know about obesity-induced impairments in immune function, we want to know whether these can be reversed by interventions, such as diet and exercise," she said. "Is a person permanently immunologically impaired, or can losing weight, body fat or both, reverse the effects, or is some other mechanism involved?" Such studies involving diet and exercise currently are underway in animals.