Zingoni Alessandra, Fionda Cinzia, Borrelli Cristiana, Cippitelli Marco, Santoni Angela, Soriani Alessandra
Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
Front Immunol. 2017 Sep 25;8:1194. doi: 10.3389/fimmu.2017.01194. eCollection 2017.
Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i.e., mitotic catastrophe, senescence, and autophagy). However, it is becoming increasingly clear that they can trigger additional stress responses. Indeed, relevant immunostimulating effects of different therapeutic programs include also the activation of pathways able to promote their recognition by immune effector cells. Among stress-inducible immunostimulating proteins, changes in the expression levels of NK cell-activating and inhibitory ligands, as well as of death receptors on tumor cells, play a critical role in their detection and elimination by innate immune effectors, including NK cells. Here, we will review recent advances in chemotherapy-mediated cellular stress pathways able to stimulate NK cell effector functions. In particular, we will address how these cytotoxic lymphocytes sense and respond to different types of drug-induced stresses contributing to anticancer activity.
自然杀伤（NK）细胞是先天性细胞毒性淋巴细胞，在一种称为癌症免疫监视的过程中，积极预防肿瘤的发生、生长和转移扩散。只要癌细胞逃避免疫监视，免疫控制与肿瘤生长之间就能维持平衡。旨在杀死癌细胞并同时维持宿主抗肿瘤免疫力的疗法是控制肿瘤生长的一种有吸引力的策略。几种化疗药物，根据所使用的药物和剂量不同，可通过凋亡、免疫原性细胞死亡或其他形式的非凋亡性死亡（即有丝分裂灾难、衰老和自噬）导致DNA损伤和癌细胞死亡。然而，越来越清楚的是，它们还能引发额外的应激反应。事实上，不同治疗方案的相关免疫刺激作用还包括激活能够促进免疫效应细胞识别它们的信号通路。在应激诱导的免疫刺激蛋白中，NK细胞激活和抑制性配体以及肿瘤细胞上死亡受体的表达水平变化，在包括NK细胞在内的先天性免疫效应细胞对它们的检测和清除中起关键作用。在此，我们将综述化疗介导的能够刺激NK细胞效应功能的细胞应激信号通路的最新进展。特别是，我们将探讨这些细胞毒性淋巴细胞如何感知和应对不同类型的药物诱导应激，这些应激有助于抗癌活性。
