دورية أكاديمية
Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity.
العنوان: | Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity. |
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المؤلفون: | Carmi Y; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA., Spitzer MH; 1] School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA [2] School of Medicine, Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Palo Alto, California 94305, USA., Linde IL; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA., Burt BM; School of Medicine, Department of Cardiothoracic Surgery, Stanford University, Palo Alto, California 94305, USA., Prestwood TR; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA., Perlman N; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA., Davidson MG; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA., Kenkel JA; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA., Segal E; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA., Pusapati GV; School of Medicine, Department of Biochemistry, Stanford University, Palo Alto, California 94305, USA., Bhattacharya N; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA., Engleman EG; School of Medicine, Department of Pathology, Stanford University, Palo Alto, California 94305, USA. |
المصدر: | Nature [Nature] 2015 May 07; Vol. 521 (7550), pp. 99-104. Date of Electronic Publication: 2015 Apr 29. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
مواضيع طبية MeSH: | Antibodies, Neoplasm/*immunology , Antigens, Neoplasm/*immunology , Dendritic Cells/*immunology , Immunoglobulin G/*immunology , Neoplasms/*immunology , T-Lymphocytes/*immunology, Animals ; Antibodies, Neoplasm/administration & dosage ; CD40 Antigens/metabolism ; Disease Models, Animal ; Female ; Immunoglobulin G/administration & dosage ; Isoantibodies/administration & dosage ; Isoantibodies/immunology ; Lymphocyte Activation/immunology ; Male ; Mice ; Neoplasm Metastasis ; Neoplasm Transplantation/immunology ; Neoplasms/pathology ; Receptors, IgG/immunology ; Tumor Necrosis Factor-alpha/immunology |
مستخلص: | Whereas cancers grow within host tissues and evade host immunity through immune-editing and immunosuppression, tumours are rarely transmissible between individuals. Much like transplanted allogeneic organs, allogeneic tumours are reliably rejected by host T cells, even when the tumour and host share the same major histocompatibility complex alleles, the most potent determinants of transplant rejection. How such tumour-eradicating immunity is initiated remains unknown, although elucidating this process could provide the basis for inducing similar responses against naturally arising tumours. Here we find that allogeneic tumour rejection is initiated in mice by naturally occurring tumour-binding IgG antibodies, which enable dendritic cells (DCs) to internalize tumour antigens and subsequently activate tumour-reactive T cells. We exploited this mechanism to treat autologous and autochthonous tumours successfully. Either systemic administration of DCs loaded with allogeneic-IgG-coated tumour cells or intratumoral injection of allogeneic IgG in combination with DC stimuli induced potent T-cell-mediated antitumour immune responses, resulting in tumour eradication in mouse models of melanoma, pancreas, lung and breast cancer. Moreover, this strategy led to eradication of distant tumours and metastases, as well as the injected primary tumours. To assess the clinical relevance of these findings, we studied antibodies and cells from patients with lung cancer. T cells from these patients responded vigorously to autologous tumour antigens after culture with allogeneic-IgG-loaded DCs, recapitulating our findings in mice. These results reveal that tumour-binding allogeneic IgG can induce powerful antitumour immunity that can be exploited for cancer immunotherapy. |
التعليقات: | Comment in: Nat Rev Cancer. 2015 Jun;15(6):319. (PMID: 25998707) |
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معلومات مُعتمدة: | T32 AI007290 United States AI NIAID NIH HHS; F31 CA189331 United States CA NCI NIH HHS; 5T32AI007290-27 United States AI NIAID NIH HHS; F31CA189331 United States CA NCI NIH HHS; P30 CA124435 United States CA NCI NIH HHS; U01 CA141468 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (Antibodies, Neoplasm) 0 (Antigens, Neoplasm) 0 (CD40 Antigens) 0 (Immunoglobulin G) 0 (Isoantibodies) 0 (Receptors, IgG) 0 (Tumor Necrosis Factor-alpha) |
تواريخ الأحداث: | Date Created: 20150430 Date Completed: 20160602 Latest Revision: 20210103 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC4877172 |
DOI: | 10.1038/nature14424 |
PMID: | 25924063 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-4687 |
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DOI: | 10.1038/nature14424 |