Natural killer (NK) cells are innate lymphoid cells that play a major role in the immune surveillance against tumors and their activity is regulated through signals derived by a number of NK cell inhibitory and activating receptors as well as cytokines and other soluble factors released in the tumor microenvironment. Extracellular vesicles (EVs) are membrane-enclosed particles secreted by all cell types, both in healthy and diseased conditions, and are important mediators of intercellular communication. Depending on the molecular cargo, tumor-derived extracellular vesicles have the capability to either promote or suppress NK cell-mediated functions. Anti-cancer therapies designed to sustain host anti-tumor immune response represent an appealing strategy to control tumor growth avoiding tumor immune escape. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Moreover, the activation of the DNA damage response (DDR) and the induction of senescence represent two crucial modalities aimed at promoting the clearance of drug-treated tumor cells by NK cells. Herein, we will address the main mechanisms used by cancer-derived extracellular vesicles to modulate NK cell activity, and we will discuss how anti-cancer therapies might impact on the secretion and the immunomodulatory function of these vesicles.

中文翻译：

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癌症细胞外囊泡是NK细胞反应的新型调节剂。

天然杀伤（NK）细胞是先天性淋巴样细胞，在针对肿瘤的免疫监视中起主要作用，其活性受多种NK细胞抑制和激活受体以及细胞因子和其他可溶因子释放的信号调节。肿瘤微环境。细胞外囊泡（EVs）是在健康和患病条件下所有细胞类型分泌的膜封闭颗粒，并且是细胞间通讯的重要介体。取决于分子货物，肿瘤来源的细胞外囊泡具有促进或抑制NK细胞介导的功能的能力。设计用于维持宿主抗肿瘤免疫反应的抗癌疗法代表了一种吸引人的策略，可控制肿瘤生长，从而避免肿瘤免疫逃逸。抗癌化学疗法增强恶性细胞免疫原性的能力主要取决于免疫原性细胞死亡（ICD）的建立和损伤相关分子模式（DAMPs）的释放。此外，DNA损伤反应（DDR）的激活和衰老的诱导代表了两个关键模式，旨在促进NK细胞清除药物治疗的肿瘤细胞。在本文中，我们将探讨癌症来源的细胞外小泡调节NK细胞活性的主要机制，并讨论抗癌疗法可能如何影响这些小泡的分泌和免疫调节功能。