Is interleukin‐1 a good or bad ‘guy’ in tumor immunobiology and immunotherapy?

Abstract

The interleukin-1 (IL-1) family consists of two major agonistic proteins, IL-1alpha and IL-1beta, which are pleiotropic and affect mainly inflammation, immunity, and hemopoiesis. The IL-1 receptor antagonist (IL-1Ra) is a physiological inhibitor of pre-formed IL-1. In their secreted form, IL-1alpha and IL-1beta bind to the same receptors and induce the same biological functions. However, the IL-1 molecules differ in their compartmentalization within the producing cell or the microenvironment. Thus, IL-1beta is solely active in its secreted form, whereas IL-1alpha is mainly active in cell-associated forms (intracellular precursor and membrane-bound IL-1) and only rarely as a secreted cytokine, mainly by macrophages/monocytes. IL-1 is abundant at tumor sites, being produced by cellular elements of the tumor microenvironment or by the malignant cells, and it affects not only various phases of the malignant process, such as carcinogenesis, tumor growth, and invasiveness, but also patterns of interactions between malignant cells and the host's immune system. Hence, the effects of the IL-1 molecules on the malignant process are complex and are often of an opposing nature. Comparative studies on the differential roles of malignant cell- or host-derived IL-1alpha and IL-1beta in different stages of the malignant process can subsequently open new avenues for manipulation of IL-1 expression and function in cancer immunotherapy.