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探索基于自然杀伤细胞的免疫疗法靶向高级别浆液性卵巢癌的潜力。

Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.

作者信息

Kaur Kawaljit, Sanghu Jashan, Memarzadeh Sanaz, Jewett Anahid

机构信息

Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, 10833 Le Conte Ave, Los Angeles, CA 90095, USA.

Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Vaccines (Basel). 2024 Jun 18;12(6):677. doi: 10.3390/vaccines12060677.

Abstract

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors.

摘要

高级别浆液性卵巢癌(HGSOCs)可能由低分化的干细胞样细胞(PDSLCs)和分化的肿瘤细胞组成。传统疗法无法完全根除PDSLCs,从而导致疾病进展和肿瘤复发。已知原代自然杀伤细胞(NK细胞)能有效裂解PDSLCs,但它们对分化良好的肿瘤细胞的细胞毒性潜力较低或几乎没有。在本综述中,我们介绍并讨论了超活化NK(sNK)细胞的特性。与原代NK细胞相比,sNK细胞对PDSLCs和分化良好的肿瘤细胞的直接杀伤能力显著更高。此外,sNK细胞分泌的细胞因子水平显著更高,尤其是那些已知能诱导肿瘤细胞分化的细胞因子。此外,我们提出sNK细胞与化疗联合可能是消除卵巢肿瘤异质性群体最有效的策略之一;sNK细胞既能裂解PDSLCs,也能裂解分化良好的肿瘤细胞,诱导PDSLCs分化,并且可与化疗联合用于靶向分化良好的肿瘤细胞以及由NK细胞诱导分化的肿瘤细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ca/11209217/b77dc8837e8f/vaccines-12-00677-g001.jpg

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