Agonists for cytosolic bacterial receptor ALPK1 induce antitumour immunity
Ribas, A. et al. SD-101 in combination with pembrolizumab in advanced melanoma: results of a phase Ib, multicenter study. Cancer Discov. 8, 1250–1257 (2018).
Google Scholar
Ackerman, S. E. et al. Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity. Nat. Cancer 2, 18–33 (2021).
Google Scholar
Ramanjulu, J. M. et al. Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature 564, 439–443 (2018).
Google Scholar
Pan, B. S. et al. An orally available non-nucleotide STING agonist with antitumor activity. Science 369, eaba6098 (2020).
Zhou, P. et al. Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. Nature 561, 122–126 (2018).
Google Scholar
Zimmermann, S. et al. ALPK1– and TIFA-dependent innate immune response triggered by the Helicobacter pylori type IV secretion system. Cell Rep. 20, 2384–2395 (2017).
Google Scholar
Milivojevic, M. et al. ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-bisphosphate of gram-negative bacteria. PLoS Pathog. 13, e1006224 (2017).
Google Scholar
Williams, L. B. et al. ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder. Genet. Med. 21, 2103–2115 (2019).
Google Scholar
Boulard, O., Kirchberger, S., Royston, D. J., Maloy, K. J. & Powrie, F. M. Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation. J. Exp. Med. 209, 1309–1324 (2012).
Google Scholar
Ryzhakov, G. et al. Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis. Nat. Commun. 9, 3797 (2018).
Google Scholar
Buettner, M. & Bleich, A. Mapping colitis susceptibility in mouse models: distal chromosome 3 contains major loci related to Cdcs1. Physiol. Genom. 45, 925–930 (2013).
Google Scholar
Ermann, J. et al. Severity of innate immune-mediated colitis is controlled by the cytokine deficiency-induced colitis susceptibility-1 (Cdcs1) locus. Proc. Natl Acad. Sci. USA 108, 7137–7141 (2011).
Google Scholar
Corrales, L., Matson, V., Flood, B., Spranger, S. & Gajewski, T. F. Innate immune signaling and regulation in cancer immunotherapy. Cell Res. 27, 96–108 (2017).
Google Scholar
Demaria, O. et al. Harnessing innate immunity in cancer therapy. Nature 574, 45–56 (2019).
Google Scholar
Tang, Y. et al. The beta-d-manno-heptoses are immune agonists across kingdoms. Science 385, 678–684 (2024).
Google Scholar
Cui, J. et al. The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells. PLoS Pathog. 17, e1009787 (2021).
Google Scholar
Faass, L., Hauke, M., Stein, S. C. & Josenhans, C. Innate immune activation and modulatory factors of Helicobacter pylori towards phagocytic and nonphagocytic cells. Curr. Opin. Immunol. 82, 102301 (2023).
Google Scholar
Pfannkuch, L. et al. ADP heptose, a novel pathogen-associated molecular pattern identified in Helicobacter pylori. FASEB J. 33, 9087–9099 (2019).
Google Scholar
Martin-Gallausiaux, C. et al. Akkermansia muciniphila upregulates genes involved in maintaining the intestinal barrier function via ADP-heptose-dependent activation of the ALPK1/TIFA pathway. Gut Microbes 14, 2110639 (2022).
Google Scholar
Martin-Gallausiaux, C. et al. Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation. Gut Microbes 16, 2295384 (2024).
Google Scholar
Kozycki, C. T. et al. Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome. Ann. Rheum. Dis. 81, 1453–1464 (2022).
Google Scholar
Jamilloux, Y. et al. ALPK1 gene mutations drive autoinflammation with ectodermal dysplasia and progressive vision loss. J. Clin. Immunol. 41, 1671–1673 (2021).
Google Scholar
Zhong, L. et al. Juvenile onset splenomegaly and oculopathy due to germline mutation in ALPK1. J. Clin. Immunol. 40, 350–358 (2020).
Google Scholar
Sun, Z. et al. Ocular manifestations of ROSAH syndrome caused by different mutations of the ALPK1 gene. Am. J. Ophthalmol. 281, 456–464 (2025).
Sangiorgi, E. et al. Rare missense variants in the ALPK1 gene may predispose to periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Eur. J. Hum. Genet. 27, 1361–1368 (2019).
Google Scholar
Luster, A. D. & Leder, P. IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo. J. Exp. Med. 178, 1057–1065 (1993).
Google Scholar
Pertl, U. et al. IFN-γ-inducible protein-10 is essential for the generation of a protective tumor-specific CD8 T cell response induced by single-chain IL-12 gene therapy. J. Immunol. 166, 6944–6951 (2001).
Google Scholar
Dufour, J. H. et al. IFN-γ-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J. Immunol. 168, 3195–3204 (2002).
Google Scholar
Nakasone, Y. et al. Host-derived MCP-1 and MIP-1alpha regulate protective anti-tumor immunity to localized and metastatic B16 melanoma. Am. J. Pathol. 180, 365–374 (2012).
Google Scholar
Lanca, T. et al. Protective role of the inflammatory CCR2/CCL2 chemokine pathway through recruitment of type 1 cytotoxic gammadelta T lymphocytes to tumor beds. J. Immunol. 190, 6673–6680 (2013).
Google Scholar
Deshmane, S. L., Kremlev, S., Amini, S. & Sawaya, B. E. Monocyte chemoattractant protein-1 (MCP-1): an overview. J. Interferon Cytokine Res. 29, 313–326 (2009).
Google Scholar
Hildner, K. et al. Batf3 deficiency reveals a critical role for CD8α+ dendritic cells in cytotoxic T cell immunity. Science 322, 1097–1100 (2008).
Google Scholar
Bill, R. et al. CXCL9: SPP1 macrophage polarity identifies a network of cellular programs that control human cancers. Science 381, 515–524 (2023).
Google Scholar
Afik, R. et al. Tumor macrophages are pivotal constructors of tumor collagenous matrix. J. Exp. Med. 213, 2315–2331 (2016).
Google Scholar
Conlon, J. et al. Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid. J. Immunol. 190, 5216–5225 (2013).
Google Scholar
Meric-Bernstam, F. et al. Phase I dose-escalation trial of MIW815 (ADU-S100), an intratumoral STING agonist, in patients with advanced/metastatic solid tumors or lymphomas. Clin. Cancer Res. 28, 677–688 (2022).
Google Scholar
Gulen, M. F. et al. Signalling strength determines proapoptotic functions of STING. Nat. Commun. 8, 427 (2017).
Google Scholar
Larkin, B. et al. Cutting edge: activation of STING in T cells induces type I IFN responses and cell death. J. Immunol. 199, 397–402 (2017).
Google Scholar
Huang, Q. et al. The primordial differentiation of tumor-specific memory CD8+ T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes. Cell 185, 4049–4066 (2022).
Google Scholar
Vitiello, G. A. F., Ferreira, W. A. S., Cordeiro de Lima, V. C. & Medina, T. D. S. Antiviral responses in cancer: boosting antitumor immunity through activation of interferon pathway in the tumor microenvironment. Front. Immunol. 12, 782852 (2021).
Google Scholar
Zak, J. et al. JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma. Science 384, eade8520 (2024).
Google Scholar
Mathew, D. et al. Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients. Science 384, eadf1329 (2024).
Google Scholar
Morales, A., Eidinger, D. & Bruce, A. W. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J. Urol. 116, 180–183 (1976).
Google Scholar
Babjuk, M. et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur. Urol. 59, 997–1008 (2011).
Google Scholar
Snelling, T., Saalfrank, A., Wood, N. T. & Cohen, P. ALPK1 mutants causing ROSAH syndrome or Spiradenoma are activated by human nucleotide sugars. Proc. Natl Acad. Sci. USA 120, e2313148120 (2023).
Google Scholar
Zhao, Y. et al. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature 477, 596–600 (2011).
Google Scholar
Wiig, H., Tenstad, O., Iversen, P. O., Kalluri, R. & Bjerkvig, R. Interstitial fluid: the overlooked component of the tumor microenvironment? Fibrogenesis Tissue Repair 3, 12 (2010).
Google Scholar
Mayer, C. T. et al. Selective and efficient generation of functional Batf3-dependent CD103+ dendritic cells from mouse bone marrow. Blood 124, 3081–3091 (2014).
Google Scholar
■ مصدر الخبر الأصلي
نشر لأول مرة على: www.nature.com
تاريخ النشر: 2025-12-10 02:00:00
الكاتب: Xiaoying Tian
تنويه من موقع “yalebnan.org”:
تم جلب هذا المحتوى بشكل آلي من المصدر:
www.nature.com
بتاريخ: 2025-12-10 02:00:00.
الآراء والمعلومات الواردة في هذا المقال لا تعبر بالضرورة عن رأي موقع “yalebnan.org”، والمسؤولية الكاملة تقع على عاتق المصدر الأصلي.
ملاحظة: قد يتم استخدام الترجمة الآلية في بعض الأحيان لتوفير هذا المحتوى.
