Tumours are often immunogenic — they produce proteins that are not normally expressed in adult tissues and are therefore not regarded as 'self' by the immune response. Some of these genes are also expressed by germ cells, so they can be detected in the testes (which are immunoprotected). A group led by Andrew Simpson has used massively parallel signature sequencing (MPSS) to identify several new 'cancer–testis' (CT) antigens, which represent promising candidates for vaccines to augment the immune response against cancer.

The authors used MPSS to create an expression profile for various human tissues. They generated millions of short sequence tags from the 3′ regions of mRNAs expressed by human tissues and most of these tags were unambiguously assigned to individual genes. Using gene-expression databases, the authors identified those genes expressed predominantly in the testes and also expressed in CT-rich cell lines.

Using this set of testis-specific genes, the authors made real-time-PCR primers to quantify the gene expression in cancer cell lines. These 21 cell lines, which were already known to express at least one CT gene, included those derived from melanoma, sarcoma, hepatocellular carcinoma, small-cell and non-small-cell lung cancer, and colon, renal and bladder cancer.

The testis-specific genes fell into three main groups. Expression of one group was highly restricted to testes and germ-cell tumours and were not expressed in somatic tissues or non-germ-cell cancers. A second group had strong testicular expression but only marginal low-level expression in cancer lines. Both of these groups of genes probably have limited potential as vaccine targets. However, a third group represents the true CT genes; these 20 genes have strong expression in the testes and are frequently activated in cancer, probably through hypomethylation or histone deactetylation. Although there is considerable variation in the frequency with which they are expressed in cancer, it is these CT genes — which have gone undetected in other studies — that have valuable immunotherapeutic potential.

Curiously, most of the CT genes found so far — including one of those identified in the present study, called CT45 — reside on the X chromosome. Indeed, the recently completed X-chromosome sequence showed that CT gene families are a feature of this chromosome. CT45 was expressed in 13 of the 21 cell lines tested and has similar structural and expression characteristics as several important known CT vaccine candidates. The authors found that CT45 belongs to a cluster of six identical or near-identical genes, which they conclude have probably arisen through gene duplication. This distinctive X-linked CT-antigen gene family represents a set of important candidates for anticancer vaccines.