PD-1 Blockade Promotes Emerging Checkpoint Inhibitors in Enhancing T Cell Responses to Allogeneic Dendritic Cells
| العنوان: | PD-1 Blockade Promotes Emerging Checkpoint Inhibitors in Enhancing T Cell Responses to Allogeneic Dendritic Cells |
|---|---|
| المؤلفون: | Carmen Stecher, Markus Zettl, Judith Leitner, Gerhard J. Zlabinger, Christoph Höller, Katharina Grabmeier-Pfistershammer, Claire Battin, Peter Steinberger |
| المصدر: | Frontiers in Immunology, Vol 8 (2017) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media SA, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | lcsh:Immunologic diseases. Allergy, 0301 basic medicine, TIM-3, medicine.medical_treatment, T cell, Immunology, BTLA, Biology, 03 medical and health sciences, Immune system, TIGIT, LAG-3, PD-1, medicine, Immunology and Allergy, immune checkpoint, Original Research, Immune checkpoint, Blockade, 030104 developmental biology, Cytokine, medicine.anatomical_structure, CTLA-4, Cancer research, coinhibitory receptors, CD160, lcsh:RC581-607 |
| 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. |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f4ec9ea01fa5df685b161b8c21f62d55Test https://doi.org/10.3389/fimmu.2017.00572Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f4ec9ea01fa5df685b161b8c21f62d55 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
|---|