• Anne Forde

• Oncogenes and the Immune Response in Burkitt's Lymphoma

Schlee et al., pp. 1387–1395

Burkitt's Lymphoma (BL) is a high-grade malignancy, associated with Epstein-Barr virus, in which chromosomal translocation results in the deregulation of the proto-oncogene c-myc. Although BL cells express a limited number of EBV antigens, they are consistently ignored by cytotoxic T-cells (CTLS) in vivo.

On the other hand, cells of posttransplant lymphoproliferative disease (PTLD) – an EBV-driven B-cell proliferation – elicits a robust CTL response. In this report Schlee et al. tackle an unanswered question: are BLs poorly immunogenic because they do not express the full range of EBV antigens or because c-myc is overexpressed? Using EBV-immortalized cell lines as a model of PTLD and several EBV-positive BL cell lines, the authors looked at differential gene expression. EBV-immortalized cells showed high expression levels of NF-κB target genes whereas BL showed low levels. Furthermore, BL cells showed very low expression of interferon-regulated genes such as STAT1.

To pin-point the effects of c-MYC expression on immune regulators, Schlee and colleagues used cell lines in which c-MYC expression can be induced. They demonstrated that switching off c-MYC expression leads to STAT1 induction and vice versa. Furthermore, c-MYC inhibits expression of IFN- β1. Analysis of the STAT promoter showed that c-MYC could bind it directly andc-MYC could inhibit both IFN- β1-dependent and-independent STAT1 promoter activity.

This detailed study shows that c-MYC is able to downregulate key players such as STAT1 and IFN- β1 in the immune response and may explain the distinct lack of immunogenicity of BL cells.

• Coffee Consumption and Cancer

Montella et al., pp. 1555–1559

Naganuma et al., pp. 1542–1547

A protective effect of coffee drinking in the cancer risk of the digestive tract and related organs has been observed. However, the evidence across studies is inconsistent.

In this issue, two studies have investigated coffee consumption and cancer risk. The first group of researchers, based in Italy, investigated the association between coffee – a highly consumed national beverage – and tea consumption and the risk of developing hepatocellular carcinoma (HCC). Using a case control study comprising 185 HCC cases and a control patient group, the authors observed a significant trend (p= 0.02) of decreased HCC risk in subjects with increasing coffee consumption, starting with 14 cups/week. However, the odds ratios were not statistically significant even for consumption of 28 cups/week. No association was found with decaffeinated coffee or tea consumption. The study supports the hypothesis that coffee, but probably not caffeine, may protect against HCC.

The second report uses a prospective study to work out whether coffee can protect against colorectal cancer. Although previous case-control studies have supported a protective effect, evidence from prospective studies has been much less conclusive.

In this report Naganuma et al., evaluated over 38,000 people in the general Japanese population and identified 457 cases of colorectal cancer. The authors carefully analyzed hazard ratios in various subgroups of colorectal cancer according to coffee consumption. No significant decreased risk or any association was found across all subgroups and sexes. This large study should help end the debate as to whether coffee can protect against colorectal cancer.

• New Marker for Bladder Cancer

Atlasi et al., pp. 1598–1602

The cancer stem cell (CSC) hypothesis argues that only a subset of cancer cells – CSCs – initiate and maintain tumor cells. CSCs have biological properties similar to those of normal stem or progenitor cells and have a high self-renewal capacity. OCT-4, a POU domain transcription factor, is an important regulator of self-renewal and differentiation in embryonic stem cells. Although OCT-4 has been identified in human germ cell tumors, its expression in somatic cancers is not known.

To investigate whether OCT-4 is expressed in bladder cancer, Atlasi et al. analyzed over 50 tumors and normal bladder tissues and found a strong correlation between the expression of OCT-4 and the presence of a tumor. Using immunohistochemistry, OCT-4 was predominantly located in the nuclei of tumor cells and no immunoreactivity was found in the neighboring normal tissue.

Although it is still not known whether OCT-4 expression has any correlation with patients' prognosis, this is the first report of a link between the OCT-4 and bladder cancer. A link between stem cells' self-renewal regulatory genes, such as OCT-4, and somatic tumors adds more weight to the CSC hypothesis.