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.

中文翻译：

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IL1α拮抗IL1β并促进恶性肿瘤的适应性免疫排斥。

我们使用IL1β-/-，IL1α-/-和IL1R1-/-小鼠评估了IL1信号分子对恶性肿瘤生长的贡献。肿瘤在IL1R-/-和IL1α-/-小鼠中逐渐生长，但在IL1β-/-小鼠中通常不存在。观察是将肿瘤植入皮内还是静脉内注射，并且在多个不同的肿瘤谱系中都是如此。IL1β抗体可阻止野生型（WT）小鼠的肿瘤生长，但不能阻止IL1R1-/-或IL1α-/-小鼠的肿瘤生长。IL1α的抗体促进了IL1β-/-小鼠的肿瘤生长，并逆转了WT小鼠中抗IL1β的肿瘤抑制作用。CD8 + T细胞的耗竭和淋巴细胞动员的阻断消除了IL1β-/-肿瘤的抑制作用，就像将IL1β-/-小鼠与SCID或Rag1-/-小鼠杂交一样。最后，IL1β的阻滞与PD-1的阻滞协同作用，从而抑制了WT小鼠的肿瘤生长。