形状変化する免疫細胞ががん免疫療法に新たな知見をもたらす(Shape-shifting immune cells offer new insights into cancer immunotherapy)

2023-11-15

2023-11-14 ハーバード大学

Macrophages (red) infiltrating a tumor spheroid (Credit: The Mitragotri Laboratory for Drug Delivery/Harvard SEAS)

◆ハーバード大学の研究者は、臨床試験でがん治療において有望ながらも不振な結果を示すマクロファージについて、工学の視点からアプローチしました。マクロファージの特定のフェノタイプが腫瘍への移動で他よりも優れていることを、マイクロスコピーと機械学習を組み合わせて発見しました。
◆これにより、従来の治療法に用いられるM1マクロファージが移動において苦境に立たされている可能性が示唆され、形状変化の能力と移動効率の関連性が浮かび上がりました。研究者は、これがマクロファージ細胞療法の不振に対する新たな理解を提供し、治療法の改善に寄与する可能性があると述べています。

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マクロファージによる腫瘍浸潤のダイナミクス
Dynamics of macrophage tumor infiltration

Kolade Adebowale,Jennifer L Guerriero,Samir Mitragotr
Applied Physics Reviews Published:October 06 2023
DOI:https://doi.org/10.1063/5.0160924

Long-term remission in cancer patients treated with ex vivo bona fide M1-induced macrophages has been poor, and the reasons behind this are not understood. Injected M1 macrophages must physically migrate to tumors to execute their role that leads to a therapeutic benefit. However, the trafficking of macrophages to tumors has not been rigorously studied. We hypothesized that trafficking capabilities of macrophages are impacted when naïve M0 macrophages are converted into an M1 phenotype for macrophage therapy. To test this, we developed a three-dimensional assay comprising a tumor spheroid and macrophages to quantify macrophage tumor transport. Cell migration, permeability, and kinetics of tumor entry were quantitatively defined and compared between macrophage phenotypes. Our results demonstrate that compared to M0 macrophages, M1 macrophages migrate less efficiently toward the tumor spheroid and exhibit a fivefold lower tumor permeability. Live imaging data combined with unsupervised machine learning algorithms reveal that macrophage migration correlates with their shape transitions. Our studies highlight the importance of transport considerations in determining the efficacy of cell therapies. This study quantitatively demonstrates that the transport properties of macrophages in tumors depend on their phenotype.