Interleukin-1β (IL-1β) is abundant in the tumor microenvironment, where this cytokine can promote tumor growth, but also antitumor activities. We studied IL-1β during early tumor progression using a model of orthotopically introduced 4T1 breast cancer cells. Whereas there is tumor progression and spontaneous metastasis in wild-type (WT) mice, in IL-1β–deficient mice, tumors begin to grow but subsequently regress. This change is due to recruitment and differentiation of inflammatory monocytes in the tumor microenvironment. In WT mice, macrophages heavily infiltrate tumors, but in IL-1β–deficient mice, low levels of the chemokine CCL2 hamper recruitment of monocytes and, together with low levels of colony-stimulating factor-1 (CSF-1), inhibit their differentiation into macrophages. The low levels of macrophages in IL-1β–deficient mice result in a relatively high percentage of CD11b+ dendritic cells (DCs) in the tumors. In WT mice, IL-10 secretion from macrophages is dominant and induces immunosuppression and tumor progression; in contrast, in IL-1β–deficient mice, IL-12 secretion by CD11b+ DCs prevails and supports antitumor immunity. The antitumor immunity in IL-1β–deficient mice includes activated CD8+ lymphocytes expressing IFN-γ, TNF-α, and granzyme B; these cells infiltrate tumors and induce regression. WT mice with 4T1 tumors were treated with either anti–IL-1β or anti–PD-1 Abs, each of which resulted in partial growth inhibition. However, treating mice first with anti–IL-1β Abs followed by anti–PD-1 Abs completely abrogated tumor progression. These data define microenvironmental IL-1β as a master cytokine in tumor progression. In addition to reducing tumor progression, blocking IL-1β facilitates checkpoint inhibition.

ABSTRACT:In live animals, lead poisoning can be diagnosed by analyzing blood samples. For postmortem testing, blood samples are not available and analysis of liver or kidney is often used for diagnosis. Liver and kidney analysis is relatively expensive and results might not be quickly available. We examined an inexpensive, rapid method to screen animals for lead toxicosis postmortem by testing the mixture of body fluids (termed ''tissue fluids'') that pool in the body cavity at necropsy for lead. At necropsy we collected body fluid and liver samples from Common Loon (Gavia immer) and Bald Eagle (Haliaeetus leucocephalus) carcasses and determined concentrations of lead in tissue fluid using a desk-top blood lead analyzer. Concentrations of lead in liver were determined by inductively coupled plasma mass spectroscopy. There was strong correlation between tissue fluid and liver tissue lead concentrations, and receiver-operating characteristic analysis gave an area under the curve of 0.91, indicating that postmortem measurements of lead in tissue fluids can be utilized as a screening method for lead toxicosis.