自然杀伤(NK)细胞在控制癌症发展中起关键作用,进展和转移播散。然而,肿瘤细胞开发出一系列能够损害免疫系统激活和功能的策略,包括NK细胞。在这种情况下,一个主要事件是由基质细胞组成的免疫抑制肿瘤微环境(TME)的建立,骨髓来源的抑制细胞,肿瘤相关巨噬细胞,调节性T细胞和癌细胞本身。不同的免疫调节细胞浸润TME,通过释放几种免疫抑制分子或通过细胞与细胞的相互作用,导致NK细胞和其他具有效应子功能的淋巴细胞的募集受损。基质和肿瘤细胞损害NK细胞功能的不同机制已在成人实体瘤中得到特别探索,在较小的深度,在儿科环境中进行了调查和讨论。在这次审查中,我们将比较儿童和成人实体恶性肿瘤有关NK细胞抑制的各自机制,突出神经母细胞瘤和肾母细胞瘤的新关键数据,最常见的两种小儿颅外实体瘤。的确,两种肿瘤的特征都是存在通过释放免疫抑制分子起作用的基质细胞。此外,特定肿瘤细胞亚群通过可能由转录共激活因子TAZ控制的细胞间接触机制抑制NK细胞的细胞毒性功能.这些发现可能导致更有效的诊断方法,并开发针对已识别的细胞和分子靶标的新型免疫治疗策略。
Natural killer (NK) cells play a key role in the control of cancer development, progression and metastatic dissemination. However, tumor cells develop an array of strategies capable of impairing the activation and function of the immune system, including NK cells. In this context, a major event is represented by the establishment of an immunosuppressive tumor microenvironment (TME) composed of stromal cells, myeloid-derived suppressor cells, tumor-associated macrophages, regulatory T cells and cancer cells themselves. The different immunoregulatory cells infiltrating the TME, through the release of several immunosuppressive molecules or by cell-to-cell interactions, cause an impairment of the recruitment of NK cells and other lymphocytes with effector functions. The different mechanisms by which stromal and tumor cells impair NK cell function have been particularly explored in adult solid tumors and, in less depth, investigated and discussed in a pediatric setting. In this review, we will compare pediatric and adult solid malignancies concerning the respective mechanisms of NK cell inhibition, highlighting novel key data in neuroblastoma and Wilms\' tumor, two of the most frequent pediatric extracranial solid tumors. Indeed, both tumors are characterized by the presence of stromal cells acting through the release of immunosuppressive molecules. In addition, specific tumor cell subsets inhibit NK cell cytotoxic function by cell-to-cell contact mechanisms likely controlled by the transcriptional coactivator TAZ. These findings could lead to a more performant diagnostic approach and to the development of novel immunotherapeutic strategies targeting the identified cellular and molecular targets.