About this Research Topic
Knowledge gained from nearly four decades of studies on the development, antigen recognition and functional properties of iNKT cells has clearly implied many potential applications for new immunotherapies involving these unique T cells. Particularly, the anti-tumor immunotherapeutic capabilities of iNKT activation shown in a large number of animal models prompted early-phase clinical trials in various types of cancer. However, these have not yielded obvious signs of success to date. The complexity and limitations of specific ligands for activation of iNKT cells, which are mainly glycolipids related to the prototypical agonist α-galactosyl ceramide (αGC), have presented difficult problems with regard to creating effective and safe strategies for iNKT cell-based therapies. Recent and ongoing research aims to better understand the principles governing the activation and targeting of iNKT cells to harness their remarkable effector and immunoregulatory properties for the treatment of cancer and a variety of other diseases.
The drawbacks uncovered by clinical trials on the use of iNKT cells as immunotherapeutic agents in the treatment of cancers clearly reveal the need to gain a more integrated knowledge of agonist presentation and recognition by iNKT cells and the functional consequences of their activation. There is a need to develop new agonists that are optimized for specific clinical applications, and also for improved methods of formulating and delivering. Characterization of effects on immune cell populations induced by agonistic iNKT cells activation, the mechanisms that mediate secondary transactivation of other relevant cells, and the kinetics and levels of molecular and cellular effectors and mediators are essential for effective manipulation of the immune response applicable to specific challenges such as tumor therapy. A more integrated knowledge of the molecular interactions between the invariant TCR and the agonist-CD1d complex, the biophysical and dynamic parameters of loading to CD1d, and recognition at the cell membrane and how this translates into specific functional consequences would be invaluable to designing efficient agonists. Finally, a systematic study of the cellular components that determine the polarization of the response and final functional outcome, including presenting cells and responder iNKT cells subsets upon different agonists, strategies and target organs, would narrow the gap between results in animal models and the clinical translation to achieve effective applications to clinical immunotherapies.
We welcome the submission of original research articles on iNKT cell function, mechanisms and therapeutic applications, specifically in relation with cognate recognition, centered but not restricted to the following themes:
• Development and selection of better agonists for clinical use: functional and structural relation studies dissecting presentation and recognition.
• Methods of formulation and delivery: quantitative and kinetic analyses of presentation, activation and immune system reshaping in different organs
• Detail understanding of how cognate recognition translate into activation of different effector capacities, transactivation and regulation of other immune cells.
• Differential outcomes of iNKT manipulation in different animal models: contribution of different immune populations including iNKT subsets.
• Increasing the numbers and functionalities of iNKT cells in sick people.
• Targeting strategies to get iNKT cells and activators to optimal locations.
• How to avoid on-target/off-target toxicities and anergy.
• Synergism of iNKT cell approaches combined with other therapeutic strategies.
Short reviews that specifically integrate and critically compare knowledge on key areas, would also be welcome.
The drawbacks uncovered by clinical trials on the use of iNKT cells as immunotherapeutic agents in the treatment of cancers clearly reveal the need to gain a more integrated knowledge of agonist presentation and recognition by iNKT cells and the functional consequences of their activation. There is a need to develop new agonists that are optimized for specific clinical applications, and also for improved methods of formulating and delivering. Characterization of effects on immune cell populations induced by agonistic iNKT cells activation, the mechanisms that mediate secondary transactivation of other relevant cells, and the kinetics and levels of molecular and cellular effectors and mediators are essential for effective manipulation of the immune response applicable to specific challenges such as tumor therapy. A more integrated knowledge of the molecular interactions between the invariant TCR and the agonist-CD1d complex, the biophysical and dynamic parameters of loading to CD1d, and recognition at the cell membrane and how this translates into specific functional consequences would be invaluable to designing efficient agonists. Finally, a systematic study of the cellular components that determine the polarization of the response and final functional outcome, including presenting cells and responder iNKT cells subsets upon different agonists, strategies and target organs, would narrow the gap between results in animal models and the clinical translation to achieve effective applications to clinical immunotherapies.
We welcome the submission of original research articles on iNKT cell function, mechanisms and therapeutic applications, specifically in relation with cognate recognition, centered but not restricted to the following themes:
• Development and selection of better agonists for clinical use: functional and structural relation studies dissecting presentation and recognition.
• Methods of formulation and delivery: quantitative and kinetic analyses of presentation, activation and immune system reshaping in different organs
• Detail understanding of how cognate recognition translate into activation of different effector capacities, transactivation and regulation of other immune cells.
• Differential outcomes of iNKT manipulation in different animal models: contribution of different immune populations including iNKT subsets.
• Increasing the numbers and functionalities of iNKT cells in sick people.
• Targeting strategies to get iNKT cells and activators to optimal locations.
• How to avoid on-target/off-target toxicities and anergy.
• Synergism of iNKT cell approaches combined with other therapeutic strategies.
Short reviews that specifically integrate and critically compare knowledge on key areas, would also be welcome.
Keywords: iNKT agonists, iNKT activation, CD1d presentation, immune response activation, immunotherapeutic iNKT uses, cancer immunotherapy
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