NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?
NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?
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DOI：
10.1155/2016/4684268
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发表时间：
2016
影响因子：
4.1
通讯作者：
Vitale M
中科院分区：
文献类型：
--
作者：
Cantoni C;Huergo-Zapico L;Parodi M;Pedrazzi M;Mingari MC;Moretta A;Sparatore B;Gonzalez S;Olive D;Bottino C;Castriconi R;Vitale M
一些证据表明NK细胞可以在体内巡逻并在肿瘤的初始阶段消除肿瘤，但可能很难控制已建立的实体肿瘤。多种因素，包括肿瘤细胞向前侵袭/前转移表型的转变，肿瘤微环境的免疫抑制作用以及肿瘤结构的复杂性，可能导致NK细胞的作用有限。近年来，一些推测的NK细胞抑制机制已被确定；相反，NK细胞与处于不同过渡期的肿瘤细胞之间的串扰仍未得到充分探讨。然而，最近的体外研究和肿瘤活检的免疫组织化学分析表明，NK细胞不仅可以杀死肿瘤细胞，还可以影响肿瘤细胞的进化。事实上，NK细胞可能诱导肿瘤细胞改变hla - 1、PD-L1或NKG2D-L的表达，并调节其对免疫反应的易感性。此外，NK细胞可能优先位于肿瘤肿块的边界，在那里，肿瘤细胞确实可以经历上皮到间充质转化（EMT）获得前转移表型。最后，最近强调的HMGB1在EMT和扩增NK细胞募集中的作用为NK细胞对肿瘤进展的可能影响提供了进一步的线索，并促进了这一问题的新研究。
Several evidences suggest that NK cells can patrol the body and eliminate tumors in their initial phases but may hardly control established solid tumors. Multiple factors, including the transition of tumor cells towards a proinvasive/prometastatic phenotype, the immunosuppressive effect of the tumor microenvironment, and the tumor structure complexity, may account for limited NK cell efficacy. Several putative mechanisms of NK cell suppression have been defined in these last years; conversely, the cross talk between NK cells and tumor cells undergoing different transitional phases remains poorly explored. Nevertheless, recent in vitro studies and immunohistochemical analyses on tumor biopsies suggest that NK cells could not only kill tumor cells but also influence their evolution. Indeed, NK cells may induce tumor cells to change the expression of HLA-I, PD-L1, or NKG2D-L and modulate their susceptibility to the immune response. Moreover, NK cells may be preferentially located in the borders of tumor masses, where, indeed, tumor cells can undergo Epithelial-to-Mesenchymal Transition (EMT) acquiring prometastatic phenotype. Finally, the recently highlighted role of HMGB1 both in EMT and in amplifying the recruitment of NK cells provides further hints on a possible effect of NK cells on tumor progression and fosters new studies on this issue.