A Plausible Framework Reveals Potential Similarities in the Regulation of Immunity against Some Cancers and Some Infectious Agents: Implications for Prevention and Treatment.

Simple Summary: The immune system can fight foreign invaders by different means, expressed by different classes of immunity. There are two main classes: antibodies and cell-mediated immunity. Studies directed at how distinct classes of immunity are differentially generated and regulated have been ongoing for the better part of a century. Various quantitative variables of immunization, such as antigen doses, are critical, and were first identified more than fifty years ago. It was shown that lower and higher doses, respectively, lead to cell-mediated and antibody responses. The importance of these variables has stood the test of time. We argue here for a framework, the Threshold Hypothesis, that is consistent with these variables and accounts for their central role in determining the class of immunity generated. This framework leads to an understanding of many observations in the fields of tumor immunology and immunity against pathogens uniquely contained by cell-mediated attack. This understanding relies on the generalization that cancers are uniquely susceptible to cell-mediated attack. This confidence in the threshold mechanism led me to propose non-invasive and efficacious strategies to prevent and treat cancer and infectious diseases caused by pathogens uniquely susceptible to cell-mediated immunity. Different frameworks, which are currently employed to understand how immune responses are regulated, can account for different observations reported in the classical literature. I have argued that the predominant frameworks, employed over the last two/three decades to analyze the circumstances that determine whether an immune response is generated or this potential is ablated, and that determine the class of immunity an antigen induces, are inconsistent with diverse classical observations. These observations are "paradoxical" within the context of these frameworks and, consequently, tend to be ignored by most contemporary researchers. One such observation is that low and high doses of diverse types of antigen result, respectively, in cell-mediated and IgG antibody responses. I suggest these paradoxes render these frameworks implausible. An alternative framework, The Threshold Hypothesis, accounts for the paradoxical observations. Some frameworks are judged more plausible when found to be valuable in understanding findings in fields beyond their original compass. I explore here how the Threshold Hypothesis, initially based on studies with chemically well-defined and "simple antigens", most often a purified protein, can nevertheless shed light on diverse classical and more recent observations in the fields of immunity against cancer and against infectious agents, thus revealing common, immune mechanisms. Most cancers and some pathogens are best contained by cell-mediated immunity. The success of the Threshold Hypothesis has encouraged me to employ it as a basis for proposing strategies to prevent and to treat cancer and those infectious diseases caused by pathogens best contained by a cell-mediated attack. [ABSTRACT FROM AUTHOR]