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Updated: Jan 25, 2026

Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
Focused Ultrasound Improves NK-92MI Cells Infiltration Into Tumors
Chaopin Yang1,2, Meng Du1,2, Fei Yan3
1Department of Ultrasound Medicine, Laboratory of Ultrasound Molecular Imaging, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Abstract:
The efficiency of natural killer (NK) cells, adoptively transferred, for treatment against solid tumors is hindered by their difficulty to enter tumors from the blood circulation as well as their inability to prolong viability in the absence of IL-2. Among different sources of NK cells, we used genetically modified NK-92MI cells, a suitable candidate which can release IL-2 to maintain their viability and overcome undesirable side effects caused by systemic administration of exogenous IL-2. In this study, we evaluated whether the combination of focused ultrasound (FUS) and microbubbles can improve adoptively NK-92MI cell infiltration into ovarian tumors through biodistribution, immunofluorescence, and flow cytometry. The treatment effects of using this strategy twice a week were explored. The potential molecular mechanism of FUS assisting NK cell therapy was also initially explored through evaluating the expression of ICAM1 and CX3CL1 by qRT-PCR. Our results indicated that FUS and microbubbles can improve NK-92MI cells' infiltration into tumors, and the combination of FUS and NK-92MI cells had a better treatment effect compared to the PBS group, but not compared to the NK-92MI group. The qRT-PCR results also showed that CX3CL1 may be involved in the process of FUS-assisted NK cell infiltration. These results indicate that further optimization of the FUS-assisted strategy is still needed to achieve therapeutic benefit.
Insights
Focused ultrasound (FUS) with microbubbles enhanced natural killer (NK) cell infiltration into ovarian tumors. While improving tumor homing, the combined therapy requires further optimization for significant therapeutic benefit in solid tumor treatment.
Area of Science:
- Oncology
- Immunotherapy
- Biomedical Engineering
Background:
- Adoptively transferred natural killer (NK) cells face challenges in solid tumor treatment, including poor tumor infiltration and limited viability without IL-2.
- Genetically modified NK-92MI cells can self-sustain viability via IL-2 release, mitigating risks of exogenous IL-2 administration.
Purpose of the Study:
- To evaluate if focused ultrasound (FUS) combined with microbubbles enhances NK-92MI cell infiltration into ovarian tumors.
- To explore the therapeutic effects and potential molecular mechanisms of this FUS-assisted NK cell therapy.
Main Methods:
- Utilized biodistribution, immunofluorescence, and flow cytometry to assess NK-92MI cell infiltration.
- Administered FUS and microbubbles twice weekly in combination with NK-92MI cells.
- Investigated molecular mechanisms by evaluating ICAM1 and CX3CL1 expression using qRT-PCR.
Main Results:
- FUS and microbubbles significantly improved NK-92MI cell infiltration into ovarian tumors.
- The combination of FUS and NK-92MI cells showed improved treatment effects compared to the PBS control group.
- CX3CL1 expression was identified as potentially involved in FUS-assisted NK cell infiltration.
Conclusions:
- FUS and microbubbles can enhance the infiltration of adoptively transferred NK-92MI cells into solid tumors.
- The current FUS-assisted strategy requires further optimization to achieve a clinically relevant therapeutic benefit.
- CX3CL1 may play a role in facilitating NK cell homing to tumors under FUS treatment.
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