College of Medicine, The Pennsylvania State University Medical Center, Hershey, PA, USA.
The Penn State Melanoma and Skin Cancer Center, The Pennsylvania State University Medical Center, Hershey, PA, USA.
Immunology. 2019 Jan;156(1):47-55. doi: 10.1111/imm.13016. Epub 2018 Nov 22.
The role of aldehyde dehydrogenase (ALDH) in carcinogenesis and resistance to cancer therapies is well known. Mounting evidence also suggests a potentially important role for ALDH in the induction and function of regulatory T (Treg) cells. Treg cells are important cells of the immune system involved in promoting immune tolerance and preventing aberrant immune responses to beneficial or non-harmful antigens. However, Treg cells also impair tumor immunity, leading to the progression of various carcinomas. ALDH expression and the subsequent production of retinoic acid by numerous cells, including dendritic cells, macrophages, eosinophils and epithelial cells, seems important in Treg induction and function in multiple organ systems. This is particularly evident in the gastrointestinal tract, pulmonary tract and skin, which are exposed to a myriad of environmental antigens and represent interfaces between the human body and the outside world. Expression of ALDH in Treg cells themselves may also be involved in the proliferation of these cells and resistance to certain cytotoxic therapies. Hence, inhibition of ALDH expression may be useful to treat cancer. Besides the direct effect of ALDH inhibition on carcinogenesis and resistance to cancer therapies, inhibition of ALDH could potentially augment the immune response to tumor antigens by inhibiting Treg induction, function and ability to promote immune tolerance to tumor cells in multiple cancer types.
醛脱氢酶（ALDH）在癌症发生和对癌症治疗的耐药性中的作用是众所周知的。越来越多的证据表明，ALDH 在诱导和调节性 T（Treg）细胞功能中可能具有重要作用。Treg 细胞是免疫系统中的重要细胞，参与促进免疫耐受和防止对有益或无害抗原的异常免疫反应。然而，Treg 细胞也会损害肿瘤免疫，导致各种癌的进展。ALDH 的表达以及随后许多细胞（包括树突状细胞、巨噬细胞、嗜酸性粒细胞和上皮细胞）产生的视黄酸似乎在多个器官系统的 Treg 诱导和功能中很重要。这在胃肠道、呼吸道和皮肤中尤为明显，这些组织暴露于无数的环境抗原中，并且是人体与外界之间的界面。Treg 细胞本身中 ALDH 的表达也可能参与这些细胞的增殖和对某些细胞毒性治疗的耐药性。因此，抑制 ALDH 的表达可能有助于治疗癌症。除了 ALDH 抑制对癌症发生和对癌症治疗的耐药性的直接影响外，抑制 ALDH 还可能通过抑制 Treg 的诱导、功能以及促进对多种癌症类型中肿瘤细胞的免疫耐受的能力，增强对肿瘤抗原的免疫反应。
