Cancer/testis antigens and urological malignancies

Abstract

Cancer/testis antigens (CTAs) are a group of tumour-associated antigens (TAAs) that display normal expression in the adult testis--an immune-privileged organ--but aberrant expression in several types of cancers, particularly in advanced cancers with stem cell-like characteristics. There has been an explosion in CTA-based research since CTAs were first identified in 1991 and MAGE-1 was shown to elicit an autologous cytotoxic T-lymphocyte (CTL) response in a patient with melanoma. The resulting data have not only highlighted a role for CTAs in tumorigenesis, but have also underscored the translational potential of these antigens for detecting and treating many types of cancers. Studies that have investigated the use of CTAs for the clinical management of urological malignancies indicate that these TAAs have potential roles as novel biomarkers, with increased specificity and sensitivity compared to those currently used in the clinic, and therapeutic targets for cancer immunotherapy. Increasing evidence supports the utilization of these promising tools for urological indications.

Figure 1

Schematic diagram of an immunotherapeutic approach to treating urological malignancies that utilizes immunogenic peptides corresponding to CTAs. A tumour sample is profiled for CTA expression using DNA microarrays. A CTA ‘fingerprint’ is generated and immunogenic peptides corresponding to the CTAs are generated that are used to pulse in vitro immature dendritic cells isolated from the patient. The pulsed cells mature into professional antigen presenting cells, which are then injected back into the patient to trigger an immune response. Abbreviations: CTA, cancer/testis antigen; Cy3, cyanine 3; Cy5, cyanine 5.

Figure 2

Normalized expression heat maps. a | CT-X genes and b | non-X CT genes based on expression profiles from prostate cancer, bladder cancer, renal cell carcinoma, and testicular germ cell tumour samples (n = 397) obtained from the Gene Expression Omnibus (GEO) database. The complete list of expression profiles, together with the respective GEO dataset (GDS) records, is provided in the Supplementary Information online. The raw data files were converted into expression profiles via the GeneChip Robust Multi-Array Analysis method. Data analyses were performed using R packages, Bioconductor, and gplots. For each gene, the expression values from all samples were averaged for each type of urological malignancy. Mean expression levels for all genes were then normalized to range from 0 to 1. Some genes appear multiple times in this list as a result of different probes present on the chip.*Multiple genes involved.

Figure 3

Schematic diagram of mammalian spermatogenesis that depicts the stages of testicular germ cell tumour development. Primordial germ cells enter the testis during embryogenesis and develop into gonocytes. These cells, which are only present before birth, are thought to be the precursors of seminomas and nonseminomas. In humans, the process of spermatogenesis begins at puberty, from precursor cells known as spermatogonia, and continues throughout the adult life. Spermatocytic seminoma is thought to develop from spermatogonia or spermatoytes.