Chemoimmunotherapy: an emerging strategy for the treatment of malignant mesothelioma.

Whether the immune system can recognize malignant and premalignant cells and eliminate them to prevent the development of cancer is still a matter of open debate, but in our view, the balance of evidence favours this concept. Nonetheless, the International Agency for Research on Cancer has now predicted that cancer will overtake heart disease as the leading cause of death worldwide by 2010, showing that this protective mechanism often fails. Malignant mesothelioma has traditionally been considered a relatively non-immunogenic cancer. However, mesothelioma cells do express a set of well-defined tumour antigens that have been shown to engage with the host immune system. Mesothelioma should therefore be considered a target for immunotherapy. A variety of anticancer immunotherapies have been investigated in mesothelioma and in other malignancies, although these have been largely ineffective when used in isolation. Over recent years, there has been increasing interest in the possibility of combining immunotherapy with chemotherapy in the fight against cancer. Here, we discuss the rationale behind combining these two, long considered antagonistic, treatment options in the context of malignant mesothelioma.

Mesothelial cells: their structure, function and role in serosal repair.

The mesothelium is composed of an extensive monolayer of specialized cells (mesothelial cells) that line the body's serous cavities and internal organs. Traditionally, this layer was thought to be a simple tissue with the sole function of providing a slippery, non-adhesive and protective surface to facilitate intracoelomic movement. However, with the gradual accumulation of information about serosal tissues over the years, the mesothelium is now recognized as a dynamic cellular membrane with many important functions. These include transport and movement of fluid and particulate matter across the serosal cavities, leucocyte migration in response to inflammatory mediators, synthesis of pro-inflammatory cytokines, growth factors and extracellular matrix proteins to aid in serosal repair, release of factors to promote both the deposition and clearance of fibrin, and antigen presentation. Furthermore, the secretion of molecules, such as glycosaminoglycans and lubricants, not only protects tissues from abrasion, but also from infection and possibly tumour dissemination. Mesothelium is also unlike other epithelial-like surfaces because healing appears diffusely across the denuded surface, whereas in true epithelia, healing occurs solely at the wound edges as sheets of cells. Although controversial, recent studies have begun to shed light on the mechanisms involved in mesothelial regeneration. In the present review, the current understanding of the structure and function of the mesothelium and the biology of mesothelial cells is discussed, together with recent insights into the mechanisms regulating its repair.