論文 - 詳細
| RRC ID | 85954 |
|---|---|
| 著者 | De Ponte Conti B, Marino R, Rezzonico-Jost T, Forcato M, Mangani D, Notario E, Gargari G, Carelli E, Rinaldi A, Raimondi A, Moro S, Marzano M, Visci G, Perruzza L, Raneri M, Dallavalle D, Mantegazza G, Montani L, Prisco F, Takur R, Geginat J, Seehusen F, Notarbartolo S, Pesole G, Bicciato S, Guglielmetti S, Grassi F. |
| タイトル | Secretory IgA amplification during immune checkpoint blockade enhances the control of tumor growth by enterotropic T cells. |
| ジャーナル | Sci Adv |
| Abstract |
The gut microbiota is essential for many aspects of host physiology, and secretory immunoglobulin A (sIgA) modulates its function. The microbiota community determines the efficacy of immune checkpoint blockade (ICB) in cancer immunotherapy; however, mechanisms able to improve this function are not known. Extracellular adenosine triphosphate (ATP) released by the microbiota restricts the sIgA repertoire by limiting T follicular helper (TFH) cell activity in the Peyer's patches via stimulation of the ionotropic P2X7 receptor. We show that sIgA amplification by oral administration of the ATP hydrolyzing enzyme apyrase corrects enteropathic features of ICB and improves therapeutic efficacy. Consistent with sIgA function in reshaping the gut ecosystem and enhancing ICB, IgA-/- mice did not show any improvement of antitumor response by apyrase administration. Mechanistically, data in mice and patients with cancer suggest that invigorated enterotropic cytotoxic T cells expressing the chemokine receptor CCR9 replenish the tumor microenvironment in a CCL25-mediated manner and control tumor growth, resulting in improved ICB efficacy. |
| 巻・号 | 11(40) |
| ページ | eaeb5308 |
| 公開日 | 2025-10-3 |
| DOI | 10.1126/sciadv.aeb5308 |
| PMID | 41042869 |
| PMC | PMC12494019 |
| MeSH | Animals Apyrase / administration & dosage Apyrase / pharmacology Cell Line, Tumor Gastrointestinal Microbiome / immunology Humans Immune Checkpoint Inhibitors* / pharmacology Immune Checkpoint Inhibitors* / therapeutic use Immunoglobulin A, Secretory* / genetics Immunoglobulin A, Secretory* / immunology Immunoglobulin A, Secretory* / metabolism Immunotherapy Mice Mice, Inbred C57BL Mice, Knockout Neoplasms* / drug therapy Neoplasms* / immunology Neoplasms* / metabolism Neoplasms* / pathology Receptors, CCR / metabolism Tumor Microenvironment / immunology |
| IF | 13.117 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 1.2 |
| リソース情報 | |
| 実験動物マウス | RBRC09256 |