دورية أكاديمية
Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy.
العنوان: | Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy. |
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المؤلفون: | Pachmayr LO; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Muehlbauer A; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Flommersfeld S; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Graml F; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Hoenninger J; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), Munich, Germany., von Baumgarten L; Department of Neurosurgery, Ludwigs-Maximilians-University (LMU), Munich, Germany., Buchholz VR; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), Munich, Germany. veit.buchholz@tum.de., Grassmann S; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), Munich, Germany. grassmaS@mskcc.org.; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. grassmaS@mskcc.org. |
المصدر: | Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2023 Sep; Vol. 72 (9), pp. 3111-3124. Date of Electronic Publication: 2023 Jun 10. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 8605732 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0851 (Electronic) Linking ISSN: 03407004 NLM ISO Abbreviation: Cancer Immunol Immunother Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Berlin : Springer Verlag Original Publication: Berlin ; New York, NY : Springer International, c1982- |
مواضيع طبية MeSH: | CD8-Positive T-Lymphocytes* , Skin Neoplasms*/pathology, Humans ; Mice ; Animals ; Receptors, Chemokine ; Immunotherapy ; Lymph Nodes ; Immunotherapy, Adoptive ; Mice, Inbred C57BL |
مستخلص: | Localization is a crucial prerequisite for immune cell function and solid tumors evade immune control by modulating immune cell infiltration into the tumor stroma. Immunosuppressive cells like regulatory T cells are attracted, while cytotoxic CD8 + T cells are excluded. Engineering CD8 + T cells with chemokine receptors is a potent strategy to turn this mechanism of directed immune cell recruitment against the tumor. Here, we utilized fluorescent tagging to track the migratory behavior of tumor-specific T cells engineered with a library of all murine chemokine receptors in vivo. We then asked whether chemokine receptor-mediated redirection of antigen-specific T cells into tumors or tumor-draining lymph nodes showed superior anti-tumoral activity. We found that both targeting approaches showed higher therapeutic efficacy than control T cells. However, multiple receptors conveying the same homing pattern did not augment infiltration. Instead, in the MC38 colon carcinoma model, anti-tumoral efficacy as well as lymph node vs. tumor-homing patterns were mostly driven by CCR4 and CCR6, respectively. Overall, our data, based on fluorescent receptor tagging, identify the tumor-draining lymph node and the tumor itself as viable targets for chemokine receptor-mediated enhancement of adoptive T cell therapy. (© 2023. The Author(s).) |
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معلومات مُعتمدة: | SFB-TRR 338/1 2021-452881907 Deutsche Forschungsgemeinschaft; SFB 1054 210592381 Deutsche Forschungsgemeinschaft; 70113918 Deutsche Krebshilfe |
فهرسة مساهمة: | Keywords: Adoptive T cell therapy; Cancer immunotherapy; Chemokine receptors; Solid tumors; Tumor homing |
المشرفين على المادة: | 0 (Receptors, Chemokine) |
تواريخ الأحداث: | Date Created: 20230610 Date Completed: 20230811 Latest Revision: 20230812 |
رمز التحديث: | 20230812 |
مُعرف محوري في PubMed: | PMC10412482 |
DOI: | 10.1007/s00262-023-03472-w |
PMID: | 37301772 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1432-0851 |
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DOI: | 10.1007/s00262-023-03472-w |