Simian virus 40 and human tumors: It is time to study mechanisms.

Several studies found simian virus 40 (SV40) in 47% to 83% of human mesotheliomas. Mesotheliomas are malignant tumors of the pleura and peritoneum, firmly associated with asbestos exposure. In this issue, Gazdar and colleagues ¿Shivapurkar et al., 1999 found that SV40 is present only in the malignant cells and not in the surrounding stromal cells. Using the microdissection technique, they found SV40 in 54% of 93 mesotheliomas of the epithelial type. The surrounding reactive stromal cells, (20 lung cancers and 14 mesotheliomas of the sarcomatoid/fibrous type) did not contain SV40, confirming the specificity of their positive findings. Furthermore, SV40 was found in 14% of 14 non-malignant reactive mesothelial cell proliferations. In 12 cases of mesothelioma a noninvasive (or in situ) component was also identified. In all four cases in which SV40 sequences were present in the invasive component, sequences were also present in the accompanying noninvasive component. These data suggest that the virus resides in the mesothelial cells prior to tumor development. The data address the remaining concerns raised at an International Meeting organized by the NIH, FDA, and CDC in 1997 to definitively associate SV40 with human mesothelioma. It is time now to investigate the pathogenic mechanisms of this association, and if SV40-infected mesothelial cells are more susceptible to other carcinogens, such as asbestos. Furthermore, we must investigate the interaction between the host immune system and SV40-infected mesothelial cells, and study if the immunosuppressive activity of asbestos interferes with tumor rejection. These studies should lead to a better understanding of mesothelioma pathogenesis, and possibly to new therapeutic approaches aimed at interfering with the expression of the SV40 genome and/or at eliciting a strong immune response against SV40 infected mesothelial cells. Copyright 1999 Wiley-Liss, Inc.