Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a dismal 5-year survival rate of less than 10%.1 Despite significant advances in cancer treatment over the past decades, PDAC has stubbornly defied progress, with most patients showing limited response to standard chemotherapy regimens. Perhaps most disappointingly, the revolutionary success of immunotherapy in various cancer types has not translated to PDAC, with checkpoint inhibitors and other immunomodulatory strategies showing dismally low response rates.2 This lack of efficacy is thought to be largely due to the characteristic PDAC tumour microenvironment (TME) that contributes to make this cancer immunologically ‘cold’.3 Characterised by a dense stromal compartment, low T cell infiltration and an overall immunosuppressive microenvironment, PDACs present a formidable barrier to the immune system that ultimately explains the inefficiency of current immunotherapeutic approaches. Whether and to what extent strategies can be identified to convert these ‘cold’ tumours into ‘hot’ ones and ultimately improve immune checkpoint blockade (ICB) efficacy in PDAC remains to be determined. One such strategy leverages the impact of epigenetic regulators in the control of genomic transposable elements, which comprise retrotransposons (or retroelements, including endogenous retroviruses, ERVs) and DNA transposons.4 Indeed, one …

中文翻译：

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利用基因组逆转录元件的拉锯战来增强胰腺癌的免疫治疗


胰腺导管腺癌 （PDAC） 仍然是最致命的恶性肿瘤之一，5 年生存率不到 10%。尽管过去几十年癌症治疗取得了重大进展，但 PDAC 顽固地违抗了进展，大多数患者对标准化疗方案的反应有限。也许最令人失望的是，免疫疗法在各种癌症类型中的革命性成功并未转化为 PDAC，检查点抑制剂和其他免疫调节策略的反应率低得令人沮丧。这种疗效的缺乏被认为是由于特征性的 PDAC 肿瘤微环境 （TME） 导致这种癌症在免疫学上“冷”.3 其特征是致密的基质隔室， PDAC 具有低 T 细胞浸润性和整体免疫抑制微环境，对免疫系统构成了强大的屏障，这最终解释了当前免疫治疗方法的低效性。是否可以确定将这些“冷”肿瘤转化为“热”肿瘤并最终提高 PDAC 中免疫检查点阻断 （ICB） 疗效的策略以及确定的程度仍有待确定。其中一种策略利用了表观遗传调节因子在控制基因组转座因子方面的影响，这些因子包括反转录转座子（或逆转录因子，包括内源性逆转录病毒，ERV）和 DNA 转座子4。