小柯机器人

美国匹兹堡大学医学院Marlies Meisel研究小组发现，瘤内乳杆菌释放的膳食色氨酸代谢物促进免疫检查点抑制剂的治疗。这一研究成果于2023年4月6日在线发表在国际学术期刊《细胞》上。

研究人员阐明了益生菌释放的芳香烃受体（AhR）激动剂吲哚-3-甲醛（I3A）和肿瘤微环境中的CD8 T细胞之间的关键微生物-宿主交流，该交流可有效增强抗肿瘤免疫力并促进临床前黑色素瘤的免疫检查点抑制剂（ICI）。研究结果显示，益生菌罗伊氏乳杆菌（Lr）会转移到黑色素瘤内，在黑色素瘤内定植并持续存在，通过其释放的饮食色氨酸分解物I3A，它在局部促进产生干扰素-γ的CD8 T细胞，从而增强ICI。此外，Lr分泌的I3A是驱动抗肿瘤免疫的必要条件和充分条件，CD8 T细胞内AhR信号的缺失废除了Lr的抗肿瘤作用。此外，富含色氨酸的饮食能增强Lr和ICI诱导的抗肿瘤免疫力，这依赖于CD8 T细胞的AhR信号。最后，研究结果提示I3A在促进ICI疗效和晚期黑色素瘤患者生存方面的潜在作用。

据悉，癌症患者对益生菌的使用正在增加，包括那些接受ICI治疗的患者。

附：英文原文

Title: Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment

Author: Mackenzie J. Bender, Alex C. McPherson, Catherine M. Phelps, Surya P. Pandey, Colin R. Laughlin, Jake H. Shapira, Luzmariel Medina Sanchez, Mohit Rana, Tanner G. Richie, Tahliyah S. Mims, Angela M. Gocher-Demske, Luisa Cervantes-Barragan, Steven J. Mullett, Stacy L. Gelhaus, Tullia C. Bruno, Nikki Cannon, John A. McCulloch, Dario A.A. Vignali, Reinhard Hinterleitner, Alok V. Joglekar, Joseph F. Pierre, Sonny T.M. Lee, Diwakar Davar, Hassane M. Zarour, Marlies Meisel

Issue&Volume: 2023-04-06

Abstract: The use of probiotics by cancer patients is increasing, including among those undergoingimmune checkpoint inhibitor (ICI) treatment. Here, we elucidate a critical microbial-hostcrosstalk between probiotic-released aryl hydrocarbon receptor (AhR) agonist indole-3-aldehyde(I3A) and CD8 T cells within the tumor microenvironment that potently enhances antitumorimmunity and facilitates ICI in preclinical melanoma. Our study reveals that probioticLactobacillus reuteri (Lr) translocates to, colonizes, and persists within melanoma, where via its releaseddietary tryptophan catabolite I3A, it locally promotes interferon-γ-producing CD8T cells, thereby bolstering ICI. Moreover, Lr-secreted I3A was both necessary and sufficient to drive antitumor immunity, and lossof AhR signaling within CD8 T cells abrogated Lr’s antitumor effects. Further, a tryptophan-enriched diet potentiated both Lr- and ICI-induced antitumor immunity, dependent on CD8 T cell AhR signaling. Finally,we provide evidence for a potential role of I3A in promoting ICI efficacy and survivalin advanced melanoma patients.

DOI: 10.1016/j.cell.2023.03.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00271-4