Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Biochem Biophys Res Commun. 2022 Dec 31;637:9-16. doi: 10.1016/j.bbrc.2022.11.006. Epub 2022 Nov 5.
Group 2 innate lymphoid cells (ILC2s) are resident cells and participate in innate and adaptive immunity. In the tumor microenvironment (TME), ILC2s contribute to both tumorigenesis and inhibition of tumor growth, but the true role of ILC2s in TME construction remains unclear. We show that IL-33 treatment induces an anti-tumor effect in vivo in a mouse model of melanoma in which ILC2s and CD8 T cells infiltrate into tumor tissue. This anti-tumor effect is dependent on CD8 T cells, however, IL-33 does not act directly on CD8 T cells because the cells lack ST2, the receptor for IL-33. ILC2s and CD8 T cells in tumors of IL-33-treated mice express OX40 ligand (OX40L) and OX40, respectively, and in vivo blockade of OX40L-OX40 interaction canceled the anti-tumor effect of IL-33. Co-culture of CD8 T cells expressing OX40 with IL-33-stimulated ILC2 expressing OX40L promoted cell activation and proliferation of CD8 T cells, which was significantly suppressed by administration of anti-OX40L blocking antibody. Thus, the IL-33-ILC2 axis promotes CD8 T cell responses via OX40/OX40L interaction and exerts an anti-tumor effect.
2 型固有淋巴细胞（ILC2s）是驻留细胞，参与固有和适应性免疫。在肿瘤微环境（TME）中，ILC2s 既有助于肿瘤发生，也有助于抑制肿瘤生长，但 ILC2s 在 TME 构建中的真正作用仍不清楚。我们表明，IL-33 治疗在黑色素瘤小鼠模型中诱导了体内的抗肿瘤作用，其中 ILC2s 和 CD8 T 细胞浸润到肿瘤组织中。这种抗肿瘤作用依赖于 CD8 T 细胞，但 IL-33 不会直接作用于 CD8 T 细胞，因为这些细胞缺乏 IL-33 的受体 ST2。接受 IL-33 治疗的小鼠肿瘤中的 ILC2s 和 CD8 T 细胞分别表达 OX40 配体（OX40L）和 OX40，而体内阻断 OX40L-OX40 相互作用则取消了 IL-33 的抗肿瘤作用。表达 OX40 的 CD8 T 细胞与表达 OX40L 的 IL-33 刺激的 ILC2 共培养促进了 CD8 T 细胞的活化和增殖，而用抗-OX40L 阻断抗体给药则显著抑制了这种增殖。因此，IL-33-ILC2 轴通过 OX40/OX40L 相互作用促进 CD8 T 细胞反应，并发挥抗肿瘤作用。
