Innate Immunity Mediated by the Cytokine IL-1 Homologue 4 (IL-1H4/IL-1F7) Induces IL-12-Dependent Adaptive and Profound Antitumor Immunity

Abstract

Recently, several novel members of the IL-1 family have been identified. The possible therapeutic utility and the underlying biologic role of these new members remain unclear. In the present study we analyzed the anti-tumor activity of human IL-1 homologue 4(IL-1H4; renamed IL-F7) by adenovirus-mediated gene transfer (AdIL-1H4) directly into murine tumors. In vitro expression analysis showed that IL-1H4 was a secretory protein. Treatment of an established MCA205 mouse fibrosarcoma by single intratumoral injection of AdIL-1H4 resulted in significant growth suppression. Furthermore, complete inhibition of tumor growth was observed following multiple injections of AdIL-1H4. The anti-tumor activity of IL-1H4 was abrogated in nude and SCID mice and in IL-12-, IFN-γ-, or Fas ligand-deficient mice. In contrast, IL-1H4 was able to confer substantial anti-tumor effects in NKT-deficient mice. These results suggest that IL-1H4 could play an important role in the link between innate and adaptive immunity and may be useful for tumor immunotherapy.

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

“…IL‐37 has been identified as a natural suppressor of innate inflammatory and immune responses 8, 12. Recent studies have indicated that IL‐37 plays a protective role in tumor progression in mouse fibrosarcoma,9 human lung cancer,14, 42 hepatocellular carcinoma,13 breast cancer,43 cervical cancer,44 and renal cell carcinoma 45. Zhang et al15 found that IL‐37 inhibits colon cancer progression via β‐catenin suppression and that a lack of IL‐37 is associated with poor survival.…”

“…Nevertheless, entirely distinct with most IL‐1 family members, that are characterized with proinflammatory functions, IL‐37 has emerged as an important inhibitor of the innate immune response. With the accumulated evidence, IL‐37 has been recognized as a typical anti‐inflammatory cytokine related to autoimmune diseases, endotoxemia, inflammatory liver injury, obesity, and cancer 8, 9, 10, 11, 12. Gao et al9 found that the intratumoral injection of IL‐37 inhibited tumor growth and the antitumor activity of IL‐37 was abrogated in mice models.…”

“…With the accumulated evidence, IL‐37 has been recognized as a typical anti‐inflammatory cytokine related to autoimmune diseases, endotoxemia, inflammatory liver injury, obesity, and cancer 8, 9, 10, 11, 12. Gao et al9 found that the intratumoral injection of IL‐37 inhibited tumor growth and the antitumor activity of IL‐37 was abrogated in mice models. Moreover, the expression of IL‐37 was decreased in tumor tissues of hepatocellular carcinoma patients, and the expression level was negatively correlated with tumor size 13.…”

Delivery of Dendritic Cells Engineered to Secrete IFN-α into Central Nervous System Tumors Enhances the Efficacy of Peripheral Tumor Cell Vaccines: Dependence on Apoptotic Pathways

“…C57BL/6 mice (H-2 b ), C57BL/6-background Thy1.1 (B6.PL-Thy1 a /CyJ), perforin-deficient (C57BL/6-Pfptm1 sdz ), IFN-␥-deficient (B6129S7-ifng), and FasL-deficient (B6Smn, C3H-Fasl gld ) mice (6 -8 wk old) were purchased from The Jackson Laboratory. IL-12/IL-23 p40-deficient animals were maintained as described previously (38). Animals were handled under aseptic conditions in microisolator cages within the Central Animal Facility at the University of Pittsburgh per an Institutional Animal Care and Use Committee-approved protocol and in accordance with recommendations for the proper care and use of laboratory animals.…”

Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

“…Zhao et al and Gao et alfound that intra-tumoral injection of IL-37 leads to strong inhibition of tumor growth and this effect is dependent on T cells and B cells as it is reversed in IL-12-, IFN-γ-or Fas ligand-deficient mice and in nude and SCID mice (64,88). Yin et al showed that a single nucleotide polymorphism in the IL-37 gene (rs3811047) is significantly associated with coronary artery disease (CAD), which suggests that IL37 represents a new susceptibility gene for CAD (89).…”