How does fever benefit us?
At present, this is just a theory. For decades, studies have suggested that there is a link between history of infectious fever and lower risk of cancer — but as yet, there is no direct proof of cause.
However, in a paper now published in the journal The Quarterly Review of Biology, scientists from Nicolaus Copernicus University in Poland argue that there is a strong case for their hypothesis.
They are not the first to propose that the immune system increases resilience to cancer each time that the body fights an infectious fever.
"Several hypotheses have been presented thus far," they write, "and recent debates have pointed to the effect of fever on innate and adaptive immune functions."
They are, however, the first to single out a group of white blood cells, or lymphocytes, known as gamma-delta T cells.
Potential for cancer immunotherapy
The authors also suggest that the cells should be investigated for use in immunotherapy, which is a treatment approach that recruits and boosts the immune system to fight disease.
Research and clinical practice of immunotherapy for cancer has tended to focus on another group of white blood cells called alpha-beta T cells.
The scientists propose that a better understanding of how fever interacts with gamma-delta T cells could reveal "the larger impact and the clinical benefits of this relationship."
In the study paper, the authors review published research and data from experiments. Drawing on this, they argue that infectious fever plays a "key role" in increasing gamma-delta T cells and enhancing their "immune antitumor competence" over a person's lifespan.
They say that repeated fever responses to acute infection increase the ability of gamma-delta T cells to spot abnormal cells and cultivate environments that destroy them.
The febrile system
An infectious fever is a "defensive and adaptive reaction" by the immune system, which is triggered when the immune system encounters a particular molecular pattern, such as that of a virus or bacterium.
Recognition of the molecular pattern engages the body's "febrile system," which comprises several mechanisms.
These include, for example, "thermoregulatory mechanisms" that raise core temperature, and the release of cascades of cell signaling proteins, called cytokines, that redirect energy and resources to the immune system.
There is also a marked increase in "a vast range" of defensive immune cells called effectors. These include gamma-delta T cells, "which possess a potent anti-infectious and antitumor competence," note the authors.
Gamma-delta T cells
Gamma-delta T cells' receptor proteins are made of "gamma-delta chain heterodimers." They have been described as an "important subset of 'unconventional'" T cells.
The cells have unique features — including an "older evolutionary memory" — that enable them to carry out surveillance and attack cancer cells.
A particular group of gamma-delta T cells known as Vg9Vd2 T cells can recognize and destroy cells of many different cancers, including, for example, those of myeloma, sarcoma, carcinoma, lymphoma, and prostate cancer.
Infectious fever will considerably increase the number of Vg9Vd2 T cells circulating in the bloodstream until they account for as much as 60 percent of white bloods cells.
Given this, and the other evidence that they reviewed, the authors conclude that:
"The unique physiology of [gamma-delta] T lymphocytes [...] makes them a target for exploration in the context of fever and cancer risk, and for future cancer immunotherapy."