Gregorie Christopher J, Wiesen Jennifer L, Magner William J, Lin Athena W, Tomasi Thomas B
Roswell Park Cancer Institute, Laboratory of Molecular Medicine, Department of Immunology, Elm & Carlton Streets, Buffalo, NY 14263, USA.
J Reprod Immunol. 2009 Jul;81(1):25-33. doi: 10.1016/j.jri.2009.02.009. Epub 2009 Jun 2.
Trophoblast cells and many cancer cells that harbor foreign antigens may evade immunity by epigenetic silencing of key immune response genes, including MHC class I and II and CD40. Chromatin active agents, such as histone deacetylase inhibitors (HDACi), induce immune response gene expression but often the expression levels are low and the cells lack a robust antigen presentation response. We show here that pre-treatment of trophoblast cells and certain cancer cells with agents that activate stress pathways (Ras oncogene, PMA or H2O2) and induce senescence can substantially enhance the induction of immune response genes (MHC class II, CD40, MICA, MICB) by HDACi and restore a vigorous IFN-gamma response in trophoblast cells and tumor cells. These results could potentially impact the development of novel anti-cancer therapeutic strategies.
滋养层细胞和许多携带外来抗原的癌细胞可通过对关键免疫反应基因（包括MHC I类和II类以及CD40）进行表观遗传沉默来逃避免疫。染色质活性剂，如组蛋白去乙酰化酶抑制剂（HDACi），可诱导免疫反应基因表达，但表达水平往往较低，且细胞缺乏强大的抗原呈递反应。我们在此表明，用激活应激途径（Ras癌基因、佛波酯或过氧化氢）并诱导衰老的试剂对滋养层细胞和某些癌细胞进行预处理，可显著增强HDACi对免疫反应基因（MHC II类、CD40、MICA、MICB）的诱导，并恢复滋养层细胞和肿瘤细胞中强烈的γ干扰素反应。这些结果可能会对新型抗癌治疗策略的开发产生潜在影响。
