超音波誘導マイクロバブルで腫瘍免疫応答を向上(Ultrasound-directed microbubbles could boost immune response against tumours)

2025-01-17

2025-01-08 カナダ・コンコルディア大学

コンコルディア大学の研究チームは、超音波とマイクロバブルを用いた新しい癌治療法を提案しました。この技術は、超音波で振動するマイクロバブルがT細胞の膜透過性を増加させ、腫瘍内のT細胞を再活性化します。このプロセスにより、免疫応答を強化するサイトカインの分泌が0.1～3.6倍増加しました。この技術は非侵襲的で、将来的に免疫療法や薬物治療と組み合わせる可能性があります。この研究は「Frontiers in Immunology」に掲載されました。

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マイクロバブルを介した集束超音波によるヒトT細胞の免疫調節
Immunomodulation of human T cells by microbubble-mediated focused ultrasound

Ana Baez^,Davindra Singh^,Stephanie He^,Mehri Hajiaghayi^,Fatemeh Gholizadeh^,Peter J. Darlington^,Brandon Helfield
Frontiers in Immunology Published:22 October 2024
DOI:https://doi.org/10.3389/fimmu.2024.1486744

While met with initial and ground-breaking success targeting blood borne cancers, cellular immunotherapy remains significantly hindered in the context of solid tumors by the tumor microenvironment. Focused ultrasound, in conjunction with microbubbles, has found tremendous potential as a targeted and local drug/gene delivery technique for cancer therapy. The specific immunomodulating effects of this technique on immune cells, including T-cells, remain unexplored. Here, with freshly isolated human immune cells, we examine how focused ultrasound can viably modulate immune cell membrane permeability and influence the secretion of over 90 cytokines, chemokines and other analytes relevant to a potent immune response against cancer. We determine that microbubble-mediated focused ultrasound modulates the immune cell secretome in a time-dependent manner – ranging in ~0.1-3.6-fold changes in the concentration of a given cytokine compared to sham controls over 48 hours post-treatment (e.g. IL-1β, TNF-α, CX3CL1, CCL21). Further, we determine the general trend of a negative correlation between secreted cytokine concentration and viable ultrasound-assisted membrane permeability with negligible loss of cell viability. Taken together, the data presented here highlights the potential of microbubble-mediated focused ultrasound to viably enhance T-cell permeability and modulate key pro-immune pathways, offering a novel approach to augment targeted cellular therapies for solid tumors.