Sun Yizhe, Rodgers Furones Andrea, Gultekin Okan, Khare Shruti, Neo Shi Yong, Shi Wenyang, Moyano-Galceran Lidia, Lam Kong-Peng, Dasgupta Ramanuj, Fuxe Jonas, Salehi Sahar, Lehti Kaisa, Sarhan Dhifaf
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Biosciences (Tumor Immunology), RadboudUMC, Nijmegen, the Netherlands.
Cancer Immunol Res. 2025 Jul 2;13(7):1080-1097. doi: 10.1158/2326-6066.CIR-24-0852.
Adaptive NK (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, 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 cells, exhibit recall responses, specific cytotoxicity, and preferential infiltration into the tumor microenvironment. Our data revealed that aNK cells interact with dendritic cells within the tumor microenvironment 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 such as high-grade serous ovarian cancer, in which they resist immunosuppressive signals and maintain robust antitumor activity. This study provides new insights into the adaptive-like properties of aNK cells, underscoring their potential for advancing cancer immunotherapy strategies.
适应性自然杀伤（aNK）细胞已成为具有记忆样特性和特异性细胞毒性的自然杀伤细胞亚群，在癌症免疫治疗中具有广阔的治疗潜力。在本研究中，我们探讨了aNK细胞在高级别浆液性卵巢癌中的作用，重点关注其建立肿瘤特异性免疫记忆和有效靶向自体肿瘤的能力。通过计算机模拟、体外和离体方法相结合，我们证明，与传统自然杀伤细胞相比，aNK细胞表现出回忆反应、特异性细胞毒性以及优先浸润肿瘤微环境。我们的数据显示，aNK细胞通过HLA-E/NKG2C轴和CXCR2信号传导与肿瘤微环境中的树突状细胞相互作用，促进其记忆形成和肿瘤靶向能力。这些发现表明，aNK细胞可作为基于自然杀伤细胞的免疫疗法中的有效药物，特别是在高级别浆液性卵巢癌等实体瘤中，它们能够抵抗免疫抑制信号并维持强大的抗肿瘤活性。本研究为aNK细胞的适应性样特性提供了新见解，突出了它们在推进癌症免疫治疗策略方面的潜力。
