Jones Amber B, Rocco Abbey, Lamb Lawrence S, Friedman Gregory K, Hjelmeland Anita B
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Cancers (Basel). 2022 May 9;14(9):2339. doi: 10.3390/cancers14092339.
Under cellular distress, multiple facets of normal homeostatic signaling are altered or disrupted. In the context of the immune landscape, external and internal stressors normally promote the expression of natural killer group 2 member D (NKG2D) ligands that allow for the targeted recognition and killing of cells by NKG2D receptor-bearing effector populations. The presence or absence of NKG2D ligands can heavily influence disease progression and impact the accessibility of immunotherapy options. In cancer, tumor cells are known to have distinct regulatory mechanisms for NKG2D ligands that are directly associated with tumor progression and maintenance. Therefore, understanding the regulation of NKG2D ligands in cancer will allow for targeted therapeutic endeavors aimed at exploiting the stress response pathway. In this review, we summarize the current understanding of regulatory mechanisms controlling the induction and repression of NKG2D ligands in cancer. Additionally, we highlight current therapeutic endeavors targeting NKG2D ligand expression and offer our perspective on considerations to further enhance the field of NKG2D ligand biology.
在细胞应激状态下，正常稳态信号传导的多个方面会发生改变或中断。在免疫环境中，外部和内部应激源通常会促进自然杀伤细胞2族成员D（NKG2D）配体的表达，这些配体可使携带NKG2D受体的效应细胞群体对细胞进行靶向识别和杀伤。NKG2D配体的存在与否会严重影响疾病进展，并影响免疫治疗选择的可及性。在癌症中，已知肿瘤细胞对NKG2D配体具有独特的调节机制，这些机制与肿瘤进展和维持直接相关。因此，了解癌症中NKG2D配体的调节将有助于开展旨在利用应激反应途径的靶向治疗。在本综述中，我们总结了目前对癌症中控制NKG2D配体诱导和抑制的调节机制的理解。此外，我们强调了目前针对NKG2D配体表达的治疗努力，并就进一步加强NKG2D配体生物学领域的考虑因素提出了我们的观点。
