About this Research Topic
Natural killer (NK) cells are cytolytic immune cells with the capacity of destroying tumor cells without previous antigen presentation, making them central players in tumor surveillance. In addition, NK cells shape tumor immunity via their cross-talk with other immune cells. Thus, NK cells hold promising potential for cancer immunotherapy. However, the tumor microenvironment (TME) presents daunting challenges for NK cell response, including immunosuppressive cell-cell interactions, metabolite, and nutrient availability, and physical barriers. Therefore, a clear understanding of the regulation and activity of NK cells in the TME is crucial in order to move NK cell-based cancer immunotherapies to the first-line treatment.
The first-in-human CAR-NK cell trial in hematological cancer patients confirmed the potency and safety of employing NK cells for cancer therapy, reinvigorating the field. Besides the adoptive setting, NK cell-targeted therapies such as multi-specific engagers present promising strategies. In addition, targeting the tumor and TME itself to provide a more hospitable environment for antitumoral immune cells is increasingly garnering attention nowadays. Hence, the promise of NK cells in cancer immunotherapy is more relevant than ever. Therefore, transforming these new ideas into actionable strategies could lead to a new generation of NK-cell-based immunotherapies against solid tumors.
The aim of this Research Topic is to provide a comprehensive overview of the current insights in the trials and pressing questions of NK cell dysfunction and exhaustion in the TME and strategies to overcome these hurdles. Such knowledge will be crucial to advance NK cells to the clinical in the context of, in particular solid, tumors, either by chartering endogenous NK cells via pharmaceuticals or by engineering persistent and armored NK cells for adoptive administration.
We welcome contributions as Original Research or Review around the following subjects in fundamental, translational, and clinical settings:
- Mechanisms of NK cell suppression and evasion in the TME, mediated either directly by the tumor cells or by environmental (f)actors.
- Profiling of NK cells in the TME.
- Adoptive therapy of (engineered) NK cells for functionality in the TME.
- Direct NK cell-targeted therapy to empower NK cells in situ.
- Indirect chartering of in situ NK cells by targeting the tumor or TME.
- Experimental models mimicking the TME to study NK cells in a pathophysiological tumor context.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
The first-in-human CAR-NK cell trial in hematological cancer patients confirmed the potency and safety of employing NK cells for cancer therapy, reinvigorating the field. Besides the adoptive setting, NK cell-targeted therapies such as multi-specific engagers present promising strategies. In addition, targeting the tumor and TME itself to provide a more hospitable environment for antitumoral immune cells is increasingly garnering attention nowadays. Hence, the promise of NK cells in cancer immunotherapy is more relevant than ever. Therefore, transforming these new ideas into actionable strategies could lead to a new generation of NK-cell-based immunotherapies against solid tumors.
The aim of this Research Topic is to provide a comprehensive overview of the current insights in the trials and pressing questions of NK cell dysfunction and exhaustion in the TME and strategies to overcome these hurdles. Such knowledge will be crucial to advance NK cells to the clinical in the context of, in particular solid, tumors, either by chartering endogenous NK cells via pharmaceuticals or by engineering persistent and armored NK cells for adoptive administration.
We welcome contributions as Original Research or Review around the following subjects in fundamental, translational, and clinical settings:
- Mechanisms of NK cell suppression and evasion in the TME, mediated either directly by the tumor cells or by environmental (f)actors.
- Profiling of NK cells in the TME.
- Adoptive therapy of (engineered) NK cells for functionality in the TME.
- Direct NK cell-targeted therapy to empower NK cells in situ.
- Indirect chartering of in situ NK cells by targeting the tumor or TME.
- Experimental models mimicking the TME to study NK cells in a pathophysiological tumor context.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Keywords: Natural killer cells, Tumor microenvironment, Experimental models, Cancer, NK cell therapy, Immunosuppression, Immune evasion
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
