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