T cells are a key component of the immune system’s response to cancer. However, tumours create a hostile microenvironment that deactivates T cells, preventing them from producing cytokines—signalling molecules essential for immune activation. This suppression weakens the body’s ability to mount an effective attack against cancer cells. Finding a way to reprogram or reactivate T cells within tumours could significantly enhance cancer treatment strategies.
Researchers have developed an innovative method to enhance cancer immunotherapy using ultrasound-guided microbubbles—a technology already widely employed in medical imaging and drug delivery (Figure 1). The study explores how ultrasound can be used to modify T cell behaviour, increasing their permeability and enhancing cytokine secretion, a crucial component of the immune response against cancer. This non-invasive approach has the potential to improve existing cancer treatments by reactivating T cells that have been suppressed within the tumour microenvironment.
Figure 1. Custom-designed ultrasound treatment setup and protocol. (A) A custom-made water tank was maintained at 37°C and consisted of a cell suspension chamber position at the co-focus of two co-aligned transducers (1 MHz therapy transducer and 3.5 MHz passive cavitation detector). Suspensions of clinical Definity™ microbubbles were incubated with either human Jurkat T-cells or freshly isolated human peripheral blood mononuclear cells within the suspension chamber in either the presence or absence of FITC-dextran (10 kDa). This chamber was placed atop of magnetic stir plate to ensure homogeneity of solution, and sonicated for 2 minutes with a 1 MHz, 1000 cycle, 20% duty cycle sequence ranging in acoustic peak-negative pressure from 208-563 kPa [schematic shown in panel (B)]. (C) Schematic representation of vibrating microbubbles adjacent to immune cells (e.g. T-cell) within the suspension chamber.
Key Findings
- Reactivation of T Cells: The ultrasound and microbubble combination reversed T cell suppression, enabling them to release proteins necessary for immune activation and blood cell production. This process helps create a positive feedback loop, further amplifying the immune response.
- Time-Dependent Cytokine Secretion: The study found that cytokine release increased by 0.1 to 3.6 times compared to untreated cells over a 48-hour period. However, when ultrasound made T cell membranes more permeable, the amount of cytokines released generally decreased, indicating a complex interplay between cell permeability and cytokine production.
- Potential for Non-Invasive Cancer Therapy: The technique is entirely non-invasive, meaning it can be repeated without significant risk to the patient. Since microbubbles are already used in medical imaging, this method could be integrated into existing clinical practices, potentially transitioning from imaging to a therapeutic sequence.
The findings suggest that ultrasound-stimulated microbubbles could complement and enhance existing cancer therapies by helping T cells overcome tumour-induced suppression. Since the process is non-invasive and can be repeated, it offers a promising alternative to more aggressive treatment methods. Additionally, this technique could be combined with targeted cancer-fighting drugs to enhance tumour eradication.
While these findings are currently based on benchtop experiments, further studies will focus on refining the method for clinical applications. The research team aims to deepen their understanding of immune signalling pathways and how ultrasound-guided microbubbles can be optimised for therapeutic use.
Journal article: Ana Baez, A., et al., 2024. Immunomodulation of human T cells by microbubble-mediated focused ultrasound. Frontiers in Immunology.
Summary by Stefan Botha
