National Research Centre for Asbestos Related Diseases, QEII Medical Centre, Verdun Street, Nedlands, Perth 6009, Western Australia. ajcurrie@cyllene.uwa.edu.au

Effective antitumor CD8 T cell responses may be activated by directly targeting the innate immune system within tumors. We investigated this response by injecting a range of TLR agonists into established tumors using a mouse model of malignant mesothelioma stably transduced with the hemagglutinin (HA) gene as a marker Ag (AB1-HA). Persistent delivery of the dsRNA mimetic poly(I:C) into established AB1-HA tumors resulted in complete tumor resolution in 40% of mice, with the remaining mice also showing a significant delay in tumor progression. Experiments in athymic nude mice along with CD8 depletion and IFN-alphabeta blocking studies revealed that tumor resolution required both CD8 T cells and type I IFN induction, and was associated with local changes in MHC class I expression. Surprisingly, however, tumor resolution was not associated with systemic dissemination or tumor infiltration of effector CD8 T cells. Instead, the antitumor response was critically dependent on the reactivation of tumor-resident CD8 T cell responses. These studies suggest that, once reactivated, pre-existing local CD8 T cell responses are sufficient to resolve established tumors and that in situ type I IFN is a determining factor.

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 Centre for Cancer Research and Cell Biology, Queen’s University Belfast, 97 Liburn Road, Belfast BT9 7BL, Northern Ireland, UK. d.fennell@qub.qc.uk

Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

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Pneumologie, Hôpital d’Instruction des Armées Percy, 101 avenue Henri Barbusse, 92140 Clamart, France. j.margery@free.fr

Malignant pleural mesothelioma (MPM) remains an aggressive tumour, but medical interest has recently evolved from almost nihilism to a real interest. Significant advances are observed in the pathologic diagnosis, the staging, the knowledge of the mesothelial carcinogenesis, the identification of biological markers with potential interest in diagnosis or in treatment. Proper management implies the participation of the general population since the implementation of administrative procedures for social and economical compensation. Active and multidisciplinary therapeutic strategies are currently evaluated and the concept of multimodality treatment includes new effective chemotherapies improving survival and quality of life, modern modalities of radiotherapy and pleuropneumonectomy. This advances create hopes and interrogations because it is not currently know whether multimodality treatment will be the standard in MPM.

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Dipartimento di medicina preventiva, ambientale e del lavoro, Fondazione IRCCS-Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano. Carolina.Mensi@unimi.it

The Lombardy Mesothelioma Register (LMR) collects all incident cases of Malignant Mesothelioma (MM) occurring since January 1, 2000 in residents of the Lombardy Region. For each “possible case” reported to the Registry by Lombardy hospitals, diagnosis is ascertained through examination of clinical records (including histology reports) according to ISPESL Guidelines. For confirmed cases, a standardized questionnaire is administered to the subject or next-of-kin in order to verify the possible sources of asbestos exposure in his/her lifetime. A panel composed of industrial hygienists, occupational health physicians and occupational epidemiologists evaluate asbestos exposure in the workplace and environmental settings. Case ascertainment completeness is routinely verified using other sources such as hospital discharge records and death certificates coded as 163 (ICD IX). In the period 2000-2004, 1563 cases were collected, of whom 887 have been evaluated: the diagnosis was confirmed for 626 (70.6%) 9 out of 887 evaluated cases. The age and gender standardized incidence rate for pleural mesothelioma in the Lombardy Region, in the year 2000 (the only one with completed data), was 2.4 (males 3.7; females 1.4) per 100,000 residents/year The 70.5% of certain and probable MM has an asbestos exposure, in particular the 64.5% of cases has an occupational exposure. The experience gathered over the years by the LMR has allowed to implement an efficient information network among different institutions and health services. In addition practical skills have been gained in processing epidemiological data, a useful tool to address new scientific hypothesis and to plan ad-hoc researches. In our experience the LMR represents a potential resource transferable to the epidemiological surveillance of different occupational tumours (i.e. sino-nasal cancers).

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New York University Medical Center, Department of Surgery, 550 First Avenue, NBV-15N1, New York, NY 10016, USA. kaufma01@med.nyu.edu

Malignant pleural mesothelioma (MPM) is a rare but lethal cancer associated with asbestos exposure. Worldwide, the incidence of MPM is expected to increase over the next 20 years. The molecular and genetic profiling of MPM tumors and patients, and improved understanding of the pathogenesis of MPM may lead to novel diagnostic, preventative and therapeutic strategies. Treatment options for MPM remain limited and no consensus exists at this time. Multimodality therapy that combines surgery, chemotherapy and radiation offers the best chance for long-term survival in select patients.

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