دورية أكاديمية
Frontiers in Immunology / PD-1 Blockade Promotes Emerging Checkpoint Inhibitors in Enhancing T Cell Responses to Allogeneic Dendritic Cells
| العنوان: | Frontiers in Immunology / PD-1 Blockade Promotes Emerging Checkpoint Inhibitors in Enhancing T Cell Responses to Allogeneic Dendritic Cells |
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| المؤلفون: | Steinberger, Peter, Stecher, Carmen, Battin, Claire, Leitner, Judith, Zettl, Markus, Grabmeier-Pfistershammer, Katharina, Höller, Christoph, Zlabinger, Gerhard J. |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2017 |
| المجموعة: | MedUni Vienna ePub (Medzinische Universität Wien) |
| مصطلحات موضوعية: | PD-1, TIM-3, BTLA, CD160, LAG-3, CTLA-4, immune checkpoint, coinhibitory receptors |
| جغرافية الموضوع: | UMW:14528, UMW:14592 |
| الوصف: | Immune checkpoint inhibitors, which target coinhibitory T cell molecules to promote anticancer immune responses, are on the rise to become a new pillar of cancer therapy. However, current immune checkpoint-based therapies are successful only in a subset of patients and acquired resistances pose additional challenges. Finding new targets and combining checkpoint inhibitors might help to overcome these limitations. In this study, human T cells stimulated with allogeneic dendritic cells (DCs) were used to compare immune checkpoint inhibitors targeting TIM-3, BTLA, LAG-3, CTLA-4, and TIGIT alone or in combination with a PD-1 antibody. We found that PD-1 blockade bears a unique potency to enhance T cell proliferation and cytokine production. Other checkpoint inhibitors failed to significantly augment T cell responses when used alone. However, antibodies to TIM-3, BTLA, LAG-3, and CTLA-4 enhanced T cell proliferation in presence of a PD-1 antibody. Upregulation of coinhibitory T cell receptors upon PD-1 blockade was identified as a potential mechanism for synergistic effects between checkpoint inhibitors. Donor-specific variation in response to immune checkpoint inhibitors was attributed to the T cells rather than DCs. Additionally, we analyzed the regulation of checkpoint molecules and their ligands on T cells and allogeneic DCs in coculture, which suggested a PD-1 blockade-dependent crosstalk between T cells and APC. Our results indicate that several immune checkpoint inhibitors have the capacity to enhance T cell responses when combined with PD-1 blockade. Additional in vitro studies on human T cells will be useful to identify antibody combinations with the potential to augment T cell responses in cancer patients. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text/html |
| اللغة: | English |
| تدمد: | 1664-3224 |
| العلاقة: | vignette : https://repositorium.meduniwien.ac.at/titlepage/urn/urn:nbn:at:at-ubmuw:3-15128/128Test; urn:nbn:at:at-ubmuw:3-15128; https://resolver.obvsg.at/urn:nbn:at:at-ubmuw:3-15128Test; local:99145322734603331; system:AC15623241 |
| DOI: | 10.3389/fimmu.2017.00572 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2017.00572Test https://resolver.obvsg.at/urn:nbn:at:at-ubmuw:3-15128Test |
| حقوق: | cc-by_4 |
| رقم الانضمام: | edsbas.B1981886 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16643224 |
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| DOI: | 10.3389/fimmu.2017.00572 |