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IL1? Antagonizes IL1? and Promotes Adaptive Immune Rejection of Malignant Tumors.

ABSTRACT: We assessed the contribution of IL1 signaling molecules to malignant tumor growth using IL1?-/-, IL1?-/-, and IL1R1-/- mice. Tumors grew progressively in IL1R-/- and IL1?-/- mice but were often absent in IL1?-/- mice. This was observed whether tumors were implanted intradermally or injected intravenously and was true across multiple distinct tumor lineages. Antibodies to IL1? prevented tumor growth in wild-type (WT) mice but not in IL1R1-/- or IL1?-/- mice. Antibodies to IL1? promoted tumor growth in IL1?-/- mice and reversed the tumor-suppressive effect of anti-IL1? in WT mice. Depletion of CD8+ T cells and blockade of lymphocyte mobilization abrogated the IL1?-/- tumor suppressive effect, as did crossing IL1?-/- mice to SCID or Rag1-/- mice. Finally, blockade of IL1? synergized with blockade of PD-1 to inhibit tumor growth in WT mice. These results suggest that IL1? promotes tumor growth, whereas IL1? inhibits tumor growth by enhancing T-cell-mediated antitumor immunity.

SUBMITTER: Tian T

PROVIDER: S-EPMC7596693 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

IL1α Antagonizes IL1β and Promotes Adaptive Immune Rejection of Malignant Tumors.

Tian Tian T Lofftus Serena S Pan Youdong Y Stingley Claire A CA King Sandra L SL Zhao Jingxia J Pan Timothy Y TY Lock Rebecca R Marglous Jacob W JW Liu Kevin K Widlund Hans R HR Fuhlbrigge Robert C RC Cichowski Karen K Kupper Thomas S TS

Cancer immunology research 20200311 5

We assessed the contribution of IL1 signaling molecules to malignant tumor growth using IL1β-/-, IL1α-/-, and IL1R1-/- mice. Tumors grew progressively in IL1R-/- and IL1α-/- mice but were often absent in IL1β-/- mice. This was observed whether tumors were implanted intradermally or injected intravenously and was true across multiple distinct tumor lineages. Antibodies to IL1β prevented tumor growth in wild-type (WT) mice but not i ...[more]

PMID: 32161110

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Project description:Premature ovarian insufficiency (POI) is a significant complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. POI is particularly devastating for young girls reaching puberty, because it irreversibly affects their physical and cognitive development. Changes occurring during puberty determine their height, bone health, insulin responsiveness, lipid metabolism, cardiovascular health and cognition. The only available treatment for POI during puberty is hormone replacement therapy (HRT), which delivers non-physiological levels of estrogen, lacks other ovarian hormones and pulsatility, and is not responsive to feedback regulation. Here we report that ovarian allografts encapsulated in a hydrogel-based capsule and implanted in ovariectomized mice restore ovarian endocrine function in immune competent mice. Ovarian tissue from BALB/c mice was encapsulated in poly(ethylene-glycol) (PEG) hydrogels, with a proteolytically degradable core and a non-degradable shell. The dual capsules were implanted subcutaneously in immune competent ovariectomized C57BL/6 mice for a period of 60 days. As expected, non-encapsulated ovarian allografts implanted in a control group sensitized the recipients as confirmed with donor-specific IgG in the serum, which increased 26-fold in the 3 weeks following transplantation (p?=?0.02) and infiltration of the graft with CD8 T cells consistent with allo-immunity. In contrast, encapsulation in the Dual PEG capsules prevented sensitization to the allograft in all the recipients with no evidence of lymphocytic infiltration. In summary, the approach of hydrogel-based immunoisolation presents a minimally invasive and robust cell-therapy to restore hormonal balance in ovarian insufficiency. This report is the first to demonstrate the application of a tunable PEG-based hydrogel as an immunoisolator of allogeneic ovarian tissue to restore endocrine function in ovariectomized mice and prevent cell-mediated immune rejection in immune competent mice.

Dataset Information

IL1? Antagonizes IL1? and Promotes Adaptive Immune Rejection of Malignant Tumors.

Publications

IL1α Antagonizes IL1β and Promotes Adaptive Immune Rejection of Malignant Tumors.

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