The inverse relationship between fever and cancer

Endogenous mediators of fever redirect metabolic substrates and energy to the immune system during fever.

Turns out, recurring patterns in patients suggest the existence of an inverse relationship between the personal history of infectious fever and cancer risk, a new study reveals.

These patterns are documented throughout decades of medical literature. However, the evidence supporting this correlation continue to be primarily anecdotal.

The researchers propose a mechanistic hypothesis that focuses on the potential impact infectious fever has on a particular subset of T cells, known as gamma/delta (gd) T cells.

According to previous experiments, the authors argue that repeated exposure to fever enhances the ability of gamma delta T cells to detect cellular abnormalities and to foster inhospitable environments that destroy malignant cells. This study is the first to acknowledge the role that gd T cells may play participants in this inverse relationship.

Infectious fever is the defensive and adaptive reaction that occurs when an organism's immune system comes into contact with exogenous pyrogens, or pathogen-associated molecular pattern (PAMP). Upon recognition of these exogenous pyrogens, endogenous mediators, also known as endogenous pyrogens, engage the febrile system.

According to previous work by Shephard et al., a febrile system is composed of all of the mechanisms responsible for facilitating a fever as well as the various systems the fever affects. Thermoregulatory mechanisms are activated, resulting in the elevation of an organism's core body temperature.

The authors further elaborate on the function of endogenous mediators, like cytokines.

"In short, endogenous mediators of fever redirect metabolic substrates and energy to the immune system during fever. This markedly enhances the frequency of a vast range of immune effectors, including lymphocytes expressing gd heterodimer receptors, which possess a potent anti-infectious and antitumor competence," the authors write.

Gamma/delta T cells possess receptors comprised of gamma/delta chain heterodimer.

In fact, the authors say that the unique attributes of gd T lymphocytes lower TCR variability, fewer gene segment rearrangements, and TCRs with older evolutionary memory enable the cells to enact processes that aid in decreasing cancer risk, such as immune surveillance and attacking cancerous cells. Exposure to infection significantly expands the quantity of gd T cells. During infection, T cells can increase in number until they constitute 60 percent of the total amount of lymphocytes.

Analysis of the interaction between fever and gd T cells may generate further inquiry into the larger impact and the clinical benefits of this relationship.

The study is called 'Toward Antitumor Immunity and Febrile Infections: Gamma/Delta T Cells Hypothesis'. The authors of the study are Wieslaw Kozak, Tomasz Jedrzejewski, Malgorzata Pawlikowska, Jakub Piotrowski, and Sylwia Wrotek

The findings appeared in the Journal of Quarterly Review of Biology.

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