Toward Antitumor Immunity and Febrile Infections: Gamma/Delta (γδ) T Cells Hypothesis

Abstract

Retrospective as well as prospective clinical studies indicate that episodes of high fever as a typical reaction to an acute infection during the entire human life span are inversely related to cancer incidence. Laboratory data aimed at discovering why fever incidents appear beneficial in lowering the risk of cancer remain rudimentary at best. Several hypotheses have been presented thus far, and recent debates have pointed to the effect of fever on innate and adaptive immune functions. In this paper we focus on a particular mode of adaptive immune functioning that involves a type of T cells carrying a receptor composed of gamma/delta chain heterodimer (γδ T-cell receptor; γδ TCR). We present an argument for a key role of infectious fever in the recruitment and enhancement of immune antitumor competence of γδ T cells during the life span of a human being. The unique physiology of γδ T lymphocytes indicating a possible cellular link between innate and adaptive immunity—including modes of antigen recognition as well their presence in tissues prone to infections, metabolic stress, and neoplastic development—makes them a target for exploration in the context of fever and cancer risk, and for future cancer immunotherapy.