癌症和自身免疫性疾病通常共存，免疫检查点抑制剂疗法 (ICI) 会加剧自身免疫性疾病。我们最近描述了一种脂质肽，命名为 IK14004，它可以促进免疫抑制性 T 调节 (Treg) 细胞的扩增，并在激活 CD8 T 细胞的同时将白细胞介素 2 与干扰素 γ 的产生分离。在此，我们报告了 IK14004 介导的对 Lewis 肺癌 (LLC) 生长的抑制以及脾细胞来源的耗竭 CD4 T 细胞的重新激活。在来自健康供体的人类免疫细胞中，IK14004 调节 T 细胞受体 α/β 亚基的表达，诱导 I 型 IFN 表达，刺激自然杀伤 (NK) 细胞表达 NKG2D/NKp44 受体并增强 K562 细胞毒性。在 T 细胞和 NK 细胞中，IK14004 改变 IL-12 受体 β1/β2 链比率以有利于 IL-12p70 结合。总而言之，这种新型肽为进一步了解 ICI 免疫疗法的复杂性提供了机会，以便在不促进肿瘤逃避免疫系统的情况下最大限度地减少自身免疫反应。© 2023。作者。

Cancers and autoimmune diseases commonly co-exist and immune checkpoint inhibitor therapy (ICI) exacerbates autoimmune pathologies. We recently described a lipidic peptide, designated IK14004, that promotes expansion of immunosuppressive T regulatory (Treg) cells and uncouples interleukin-2 from interferon-gamma production while activating CD8+ T cells. Herein, we report IK14004-mediated inhibition of Lewis lung cancer (LLC) growth and re-invigoration of splenocyte-derived exhausted CD4+ T cells. In human immune cells from healthy donors, IK14004 modulates expression of the T cell receptor α/β subunits, induces Type I IFN expression, stimulates natural killer (NK) cells to express NKG2D/NKp44 receptors and enhances K562 cytotoxicity. In both T and NK cells, IK14004 alters the IL-12 receptor β1/β2 chain ratio to favour IL-12p70 binding. Taken together, this novel peptide offers an opportunity to gain further insight into the complexity of ICI immunotherapy so that autoimmune responses may be minimised without promoting tumour evasion from the immune system.© 2023. The Author(s).