ナチュラルキラー細胞が卵巣がんを記憶し効果的に標的化(Natural killer cells remember and effectively target ovarian cancer)

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2025-04-28 カロリンスカ研究所(KI)

カロリンスカ研究所の研究者たちは、特定の「適応型ナチュラルキラー細胞(aNK細胞)」が卵巣がんを記憶し、効果的に攻撃できることを発見した。aNK細胞は、過去の感染や腫瘍を覚えて強力に反応する性質を持ち、今回の研究では、卵巣がん細胞に対して浸潤・破壊活動を行う能力を持つことが確認された。この発見は、難治性がんに対する新たな免疫療法の開発に道を開く可能性がある。今後はaNK細胞を増強する臨床応用が検討される。

<関連情報>

卵巣がんにおいて適応NK細胞は腫瘍特異的免疫記憶と細胞傷害性を示す Adaptive NK Cells Exhibit Tumor-Specific Immune Memory and Cytotoxicity in Ovarian Cancer

Yizhe Sun;Andrea Rodgers Furones;Okan Gultekin;Shruti Khare;Shi Yong Neo;Wenyang Shi;Lidia Moyano-Galceran;Kong-Peng Lam;Ramanuj Dasgupta;Jonas Fuxe;Sahar Salehi;Kaisa Lehti;Dhifaf Sarhan
Cancer Immunology Research  Published:April 28 2025
DOI:https://doi.org/10.1158/2326-6066.CIR-24-0852

ナチュラルキラー細胞が卵巣がんを記憶し効果的に標的化(Natural killer cells remember and effectively target ovarian cancer)

Abstract

Adaptive Natural Killer (aNK) cells have emerged as a subset of NK cells with memory-like properties and specific cytotoxicity, offering promising therapeutic potential in cancer immunotherapy. In this study, we explored the role of aNK cells in high-grade serous ovarian cancer (HGSOC), focusing on their ability to establish tumor-specific immune memory and effectively target autologous tumors. Through a combination of in silico, in vitro, and ex vivo approaches, we demonstrated that aNK cells, in contrast to conventional NK (cNK) cells, exhibit recall responses, specific cytotoxicity, and preferential infiltration into the tumor microenvironment (TME). Our data revealed that aNK cells interact with dendritic cells (DCs) within the TME via the HLA-E/NKG2C axis and CXCR2 signaling, contributing to their memory formation and tumor-targeting capabilities. These findings suggest that aNK cells could serve as potent agents in NK cell-based immunotherapies, particularly in solid tumors like HGSOC, where they resist immunosuppressive signals and maintain robust anti-tumor activity. This study provides new insights into the adaptive-like properties of aNK cells, underscoring their potential for advancing cancer immunotherapy strategies.

医療・健康
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