Daskalos et al., pp. 81–87 Drugs that target specific enzymes involved in the epigenetic regulation of gene expression are in clinical trials for the treatment of many human cancers. In tumor cells, certain stretches of DNA, such as repeated DNA, become less methylated and more genetically active while others, especially gene promoters, are overly methylated and abnormally silenced, a condition reversed by inhibitors of DNA methyltransferases. However, it remains unclear whether these inhibitors also act on repeated DNA elements and deregulate the epigenetic control at these sites. The LINE-1 and Alu repeats are non-LTR-containing retrotransposons, which can amplify themselves via RNA intermediates and comprise a long stretch of human DNA repeat sequences. In this issue of IJC, Daskalos and colleagues examined the state of methylation of these elements in 48 primary non-small-cell lung cancer samples and found that DNA methylation was significantly reduced at both sites as compared to adjacent healthy tissues. The observed hypomethylation was widespread among tumors of variable stages, nodal metastasis and differentiation status, suggesting an early onset of this abnormality in the course of lung cancer development. In addition, the authors report that treatment with 5-aza-2′-deoxycytidine and trichostatin A, common inhibitors of DNA methylation and histone deacetylation, decreased the methylation levels of LINE-1 and Alu elements and enhanced their transcription in two lung cancer cell lines. These findings provide an intriguing link between retroelement methylation, genetic activity and genomic instability in lung cancer cells. Since active retrotransposition can induce mutations by inserting near or within genes, analysis of the activity of these elements during epigenetic treatment is now urgently needed . Hypomethylation of LINE-1 and Alu retrotransposons in lung cancer tissue (T) as compared to healthy adjacent tissue (N) from the same donor. Eaker et al., pp. 180–187 The risk of dying from breast cancer is 35% lower in women with high socioeconomic status than in socioeconomically disadvantaged women. This troubling difference persists in a national health care system intended to offer care to all on equal terms. Eaker and colleagues examined the health care system of Sweden, a single-payer system, in which the government pays almost all health care costs. They followed nearly 10,000 women registered with the Regional Breast Cancer Register of the Uppsala/Oerebro region and included variables such as cancer detection mode, tumor characteristics and primary treatment options in their population-based study. Their results support the model that differences in diagnostic intensities and treatments are not exclusively to blame for the inequalities in cancer outcome but that patient factors such as life style, general health, patient knowledge and compliance with treatment require further attention. The authors measured socioeconomic standing by educational levels. They discovered a higher proportion of large tumors and high proliferation grades among less educated women, reflecting that those tumors are detected at later stages than in women with higher education. The difference was most pronounced among women with clinically detectable tumors, pointing to the fact that women with high education may perform self-examination more often and may also take advantage of mammography examinations outside invitational screenings. The authors lobby that survival rates in the most privileged groups should set the standard for all cancer patients. Ai et al., pp. 239–244 Tumors prevent their own rejection and induce a state of immune tolerance in their host via a variety of mechanisms that include tolerogenic antigen-presenting cells, the induction of regulatory T cells (Tregs) and the secretion of immune modulatory factors. Recent experiments have shown increased frequency of Tregs in patients with a variety of cancer types and the selective recruitment and expansion of Tregs in the tumor microenvironment. Tregs isolated from tumors can suppress effector functions of cytotoxic T cells and are thought to foster an immune-privileged microenvironment within the tumor. These observations have important clinical and therapeutic implications and are supported by recent experiments showing that depletion of Tregs leads to cross-reactive tumor immunity against tumors of diverse origins. Ai and colleagues now report that follicular lymphoma B cells induce the conversion of conventional CD4+ T cells into Tregs. This effect is only observed with tumor B cells, but not with normal B cells, and it does not require any stimulation of the T-cell receptor on the developing Tregs. Importantly, T cells isolated from peripheral blood could also be converted to Tregs by tumor B cells. These observations demonstrate the existence of a novel, tumor-specific process by which tumor cells induce immune escape via the induction of Treg cells.
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Open Access
Dec 1, 2018
Mohamed Nabil Rafat + 5
