IL1α Antagonizes IL1β and Promotes Adaptive Immune Rejection of Malignant Tumors

Abstract

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 in IL1R1^-/- or IL1α^-/- mice. Antibodies to IL1α promoted tumor growth in IL1β^-/- mice and reversed the tumor-suppressive effect of anti-IL1β in WT mice. Depletion of CD8⁺ T cells and blockade of lymphocyte mobilization abrogated the IL1β^-/- tumor suppressive effect, as did crossing IL1β^-/- mice to SCID or Rag1^-/- mice. Finally, blockade of IL1β synergized with blockade of PD-1 to inhibit tumor growth in WT mice. These results suggest that IL1β promotes tumor growth, whereas IL1α inhibits tumor growth by enhancing T-cell-mediated antitumor immunity.