腫瘍細胞がどのようにして身体の免疫システムを凌駕するかに光を当てた(Researchers at UMass Amherst Shed Light on How Tumor Cells Outwit the Body’s Immune System)

2024-01-09

2024-01-08 マサチューセッツ大学アマースト校

◆マサチューセッツ大学アムハースト校の科学者チームが行った画期的な研究で、「モスキート効果」と呼ばれる現象が初めて分析され、がんの腫瘍細胞などの特定の病原体が免疫系を破る仕組みが明らかになりました。
◆この研究は、蚊が宿主の血液を摂取するのと同様に、免疫系のT細胞が腫瘍の細胞質を自身の細胞質に取り込むことを示しています。腫瘍細胞が免疫系をだます方法は以前から知られていましたが、この研究により、T細胞が腫瘍の細胞質を取り込むことが明らかになりました。これにより、がんが免疫系から逃れる仕組みが理解され、より効果的な治療への一歩が踏み出されました。

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モスキート効果:制御性T細胞およびエフェクターT細胞は細胞間移動を通じて腫瘍細胞から細胞質物質を獲得する
The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer

Kaito A. Hioki, Daniel J. Ryan, Iris Thesmar, Adam C. Lynch, Leonid A. Pobezinsky, Elena L. Pobezinskaya
Frontiers in Immunology Published:20 December 2023
DOI:https://doi.org/10.3389/fimmu.2023.1272918

The phenomenon of intercellular transfer of cellular material, including membranes, cytoplasm, and even organelles, has been observed for decades. The functional impact and molecular mechanisms of such transfer in the immune system remain largely elusive due to the absence of a robust in vivo model. Here, we introduce a new tumor mouse model, where tumor cells express the soluble ultra-bright fluorescent protein ZsGreen, which allows detection and measurement of intercellular transfer of cytoplasm from tumor cells to infiltrating immune cells. We found that in addition to various types of myeloid lineage cells, a large fraction of T regulatory cells and effector CD8 T cells acquire tumor material. Based on the distribution of tumor-derived ZsGreen, the majority of T cells integrate captured cytoplasm into their own, while most myeloid cells store tumor material in granules. Furthermore, scRNA-seq analysis revealed significant alterations in transcriptomes of T cells that acquired tumor cell cytoplasm, suggesting potential impact on T cell function. We identified that the participation of T cells in intercellular transfer requires cell-cell contact and is strictly dependent on the activation status of T lymphocytes. Finally, we propose to name the described phenomenon of intercellular transfer for tumor infiltrating T cells the “mosquito effect”.