Publications by authors named "Jorgen Kjaergaard"
Article Synopsis
- - Tumor hypoxia causes the buildup of extracellular adenosine, which activates A adenosine receptors (AR) on CD8 T cells, leading to immunosuppression and enabling tumor evasion of the immune system.
- - Research showed that deleting AR genes in mice restored CD8 T cell anti-tumor activity against less immunogenic tumors, and using AR antagonists in adoptive T cell therapy achieved similar results, suggesting a method to enhance T cell responses.
- - Targeting AR improved survival rates and established long-lasting anti-tumor immunity, highlighting both the suppressive role of AR in tumor environments and the potential of selective antagonists to enhance the effectiveness of current immunotherapy approaches.
Antitumor T cells either avoid or are inhibited in hypoxic and extracellular adenosine-rich tumor microenvironments (TMEs) by A2A adenosine receptors. This may limit further advances in cancer immunotherapy. There is a need for readily available and safe treatments that weaken the hypoxia-A2-adenosinergic immunosuppression in the TME.
View Article and Find Full Text PDFUnlabelled: Intratumoral hypoxia and hypoxia inducible factor-1α (HIF-1-α)-dependent CD39/CD73 ectoenzymes may govern the accumulation of tumor-protecting extracellular adenosine and signaling through A2A adenosine receptors (A2AR) in tumor microenvironments (TME). Here, we explored the conceptually novel motivation to use supplemental oxygen as a treatment to inhibit the hypoxia/HIF-1α-CD39/CD73-driven accumulation of extracellular adenosine in the TME in order to weaken the tumor protection. We report that hyperoxic breathing (60 % O2) decreased the TME hypoxia, as well as levels of HIF-1α and downstream target proteins of HIF-1α in the TME according to proteomic studies in mice.
View Article and Find Full Text PDFArticle Synopsis
- Cancerous tissues can protect themselves from antitumor T cells (CD8(+) and CD4(+)) due to hypoxia-induced adenosine accumulation and T regulatory cells producing adenosine, which inhibit these immune cells.
- The presence of adenosine activates A2A receptors on T cells, leading to immunosuppression, while factors like hypoxia-inducible factor-1alpha can further suppress these T cells in tumors.
- Combining anti-hypoxia strategies to reduce adenosine effects with other treatments, like CTL antigen-4 blockade, shows promise for improving immunotherapy effectiveness, as seen in studies involving mice and epidemiological data.
Article Synopsis
- Dendritic-tumor heterokaryons created through electrofusion show strong potential as immunotherapies for tumors in various organs, with single vaccinations proving effective.
- Successful tumor therapy requires an additional "third signal" from either IL-12 or an anti-OX-40R monoclonal antibody, as both enhance the immune response differently.
- The study highlights the importance of the OX-40 pathway and identifies IL-12's role in shifting immune responses from IL-10 production to effective IFN-gamma secretion, which is crucial for developing effective dendritic cell-based cancer vaccines.
Article Synopsis
- Everolimus, an mTOR inhibitor, is studied for its immunosuppressive and potential cancer-fighting properties, specifically against SCC VII squamous cell carcinoma in mice.* -
- The research involved different groups of mice receiving varying doses of everolimus and cyclosporine, measuring tumor growth and metastasis over time.* -
- Results indicated that everolimus significantly inhibited tumor growth and spread at certain doses, suggesting its potential as a safe option for immunosuppression in transplant patients with a history of cancer.*
Article Synopsis
- The study explores the potential of active immunotherapy to treat advanced malignant brain tumors in mice, highlighting its advantages over existing therapies.
- Researchers created tumor vaccines by fusing dendritic cells with irradiated tumor cells to enhance immune response and tested this treatment alongside local radiotherapy and antibodies.
- Results showed that treated mice had complete tumor regression, significantly longer survival (over 120 days), and strong immune responses without neurological side effects, suggesting a promising approach for brain tumor therapy.
Tumor-dendritic cell fusion as a basis for cancer immunotherapy.
Otolaryngol Head Neck Surg
May 2005
Article Synopsis
- The study aimed to explore the use of allogeneic dendritic-tumor fusion cells for potential cancer immunotherapy.
- Researchers created fusion cells through electrofusion using specific murine tumor lines and confirmed their success with various techniques, showing promising immune responses in mice.
- The findings suggest that these fusion cells could effectively immunize against specific tumor challenges, indicating their potential as a treatment method for head and neck cancer.
Article Synopsis
- Dendritic cells (DCs) can stimulate immune responses to tumors, but there's debate over the best ways to load them with antigens for maximum effectiveness.
- The study compared different methods of loading DCs with a specific tumor antigen using two types of DCs (mature and less mature), finding that fusing DCs with tumor cells created the most effective vaccine.
- The fusion cells not only significantly reduced tumor nodules in treated mice but also specifically stimulated immune T cells to produce IFN-gamma, showing a targeted immune response, while other preparations were less effective.
Article Synopsis
- The study explores the effectiveness of adoptive T cell therapy for treating advanced tumors, specifically how tumor-specific T cells can induce tumor regression and develop long-term memory responses.
- Thy1.2+ mice with MCA-205 tumors were treated with irradiation and received tumor-sensitized Thy1.1+ T cells, leading to the recovery of memory T cells that retained strong anti-tumor capabilities even after several months.
- The findings indicate that T cells can maintain their memory potential following ex vivo expansion, and suggests a potential strategy for enhancing immune responses against tumors in patients with ongoing disease.
Article Synopsis
- Dendritic cells (DCs) can trigger immune responses against tumors, and using DC-tumor fusion hybrids as a vaccine shows promise due to their diverse presentation of tumor antigens.
- A new electrofusion technique allowed the creation of these hybrids, which successfully eradicated tumors in various locations in mice, including the lung, skin, and brain.
- Effective immunotherapy required specific methods of vaccine delivery and co-administration of adjuvants, and the success relied on using syngeneic (genetically similar) DCs for fusion rather than allogeneic (genetically different) ones.
Article Synopsis
- Activated T cells with reduced L-selectin (L-sel(-)) from tumor-draining lymph nodes are effective in adoptive immunotherapy for tumors.* -
- In a study, these T cells showed significant proliferation after being transferred to tumor-bearing mice, peaking around day 6, and were more active in CD4 T cells compared to CD8 T cells.* -
- Successful treatment also depended on sublethal whole-body irradiation of the recipient, which helped enhance the proliferation of specific T cells at the tumor site.*
Article Synopsis
- Tumor-specific effector T cells (T(E)) can be effectively isolated and activated from the L-selectin(low) population in tumor-draining lymph nodes, leading to complete tumor rejection when transferred, particularly from day 9 (D9) samples.
- Interestingly, larger quantities of unfractionated T cells from day 12 (D12) lymph nodes failed to prevent tumor growth due to the presence of tumor-induced suppressor T cells (T(S)) that inhibit the action of T(E).
- The study reveals that the presence of these suppressor T cells, which share traits with effector T cells, can undermine the success of adoptive immunotherapy, highlighting the need to differentiate between T cell types in cancer treatments.
Article Synopsis
- Depleting these regulatory T cells using anti-CD25 monoclonal antibodies showed some ability to slow tumor growth, but tumors ultimately progressed in all mice tested.
- The research indicates that although this depletion improves the sensitization of tumor-immune T cells in draining lymph nodes, it is not enough to completely eliminate tumors, yet it aids in adoptive immunotherapy approaches.