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Migration Dynamics of Human NK Cell Preparations in Microchannels and Their Invasion Into Patient-Derived Tissue
Alina Moter1,2, Sonja Scharf3, Hendrik Schäfer3
1Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt (Main), Germany.
Abstract:
Natural killer (NK) cells are characterised by their ability to attack cancer cells without prior antigen stimulation. Additionally, clinical trials revealed great potential of NK cells expressing chimeric antigen receptors (CARs). Successful anti-tumour efficacy remains limited by migration and infiltration to the tumour site by NK cell preparations, which is linked to the scarcity in the knowledge of migration dynamics and invasion potential. Here, we applied a recently reported innovative microfluidic microchannel technology to gain insight into the intrinsic motility of NK cells. We assessed the baseline activated and proliferating NK cells in direct comparison with T cells and investigated their motility patterns in the presence of tumour cells. Additionally, we performed high-resolution 4D confocal imaging in patient-derived hyperplastic lymphatic tissues to assess their invasive capacity. Our data revealed that the invasion potential of NK cells was greater than that of T cells, despite their similar velocities. The flexibility of the NK cell nucleus may have contributed to the higher invasion potential. The motility of CD19-CAR-NK cell preparations was similar to that of non-transduced NK cells in hyperplastic lymphoid tissue, with improved targeted migration in tumour tissue, suggesting the suitability of genetically engineered NK cells for difficult-to-reach tumour tissues.
Insights
Natural killer (NK) cells show greater invasion potential than T cells, even with similar speeds. This finding, using microfluidic technology, suggests NK cells are promising for cancer immunotherapy, especially engineered CAR-NK cells.
Area of Science:
- Immunology
- Cell Biology
- Biotechnology
Background:
- Natural killer (NK) cells possess inherent anti-cancer properties without prior antigen stimulation.
- Chimeric antigen receptor (CAR) engineered NK cells show significant clinical potential for cancer therapy.
- Limited NK cell migration and infiltration to tumor sites hinder their anti-tumor efficacy, due to poorly understood migration dynamics.
Purpose of the Study:
- To investigate the intrinsic motility and invasion potential of NK cells.
- To compare NK cell migration and invasion capabilities with T cells.
- To assess the impact of tumor cells and genetic engineering (CARs) on NK cell behavior.
Main Methods:
- Utilized innovative microfluidic microchannel technology to study NK cell motility.
- Assessed baseline, activated, and proliferating NK cells against T cells.
- Employed high-resolution 4D confocal imaging in patient-derived lymphatic tissues to evaluate invasion capacity.
Main Results:
- NK cells demonstrated a greater invasion potential compared to T cells, despite comparable cell velocities.
- NK cell nuclear flexibility may contribute to their enhanced invasion capabilities.
- CD19-CAR-NK cell preparations exhibited similar motility to non-transduced NK cells in lymphoid tissue but showed improved targeted migration in tumor tissue.
Conclusions:
- NK cells possess superior intrinsic invasion potential over T cells.
- Genetic engineering with CARs does not impede NK cell motility and enhances tumor-specific migration.
- NK cells, particularly CAR-NK cells, are suitable candidates for targeting difficult-to-reach tumors in immunotherapy.

