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Hjerpe A.,Karolinska University Hospital | Ascoli V.,University of Rome La Sapienza | Bedrossian C.W.M.,Rush University | Boon M.E.,Leiden Cytology and Pathology Laboratory | And 13 more authors.
Diagnostic Cytopathology | Year: 2015

Objective To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. Data Sources Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. Rationale This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town. Diagn. Cytopathol. 2015;43:563-576. © 2015 Wiley Periodicals, Inc.

McDonnell A.M.,University of Western Australia | Prosser A.C.,University of Western Australia | Van Bruggen I.,University of Western Australia | Robinson B.W.S.,University of Western Australia | And 2 more authors.
European Journal of Immunology | Year: 2010

One of the clear paradoxes in tumor immunology is the fact that cross-presentation of cell-associated tumor antigens to CD8+ T cells is efficient, yet CTL generation is weak, and tumors continue to grow. We examined, for the first time whether this may be due to alterations in the phenotype or function of cross-presenting DC using a solid tumor model expressing a membrane bound neo-antigen (hemagglutinin, HA). Tumor antigen was constitutively cross-presented in the tumor-draining LN throughout tumor progression by CD11c+ DC. Further analysis revealed that both CD8α+ and CD8α- DC subsets, but not plasmacytoid DC, were effective at cross-presenting HA tumor antigen. The proportions of DC subsets in the tumor-draining LN were equivalent to those seen in the LN of naïve mice; however, a significant increase in the expression of the potential inhibitory B7 molecule, B7-DC, was noted and appeared to be restricted to the CD8α- DC subset. Therefore LN resident CD8α+ DC are not the sole DC subset capable of cross-presenting cell-associated tumor antigens. Migratory tumor DC subsets with altered co-stimulatory receptor expression may contribute to induction and regulation of tumor-specific responses. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

Steer H.J.,University of Western Australia | Steer H.J.,National Center for Asbestos Related Disease | Lake R.A.,University of Western Australia | Lake R.A.,National Center for Asbestos Related Disease | And 4 more authors.
Oncogene | Year: 2010

It is well established that the immune system has the capacity to attack malignant cells. During malignant transformation cells acquire numerous molecular and biochemical changes that render them potentially vulnerable to immune cells. Yet it is self-evident that a growing tumour has managed to evade these host defence mechanisms. The exact ways in which the immune system interacts with tumour cells and how cancers are able to escape immunological eradication have only recently started to be fully elucidated. Understanding the relationship between the tumour and the anti-tumour immune response and how this can be altered with conventional treatments and immune-targeted therapies is crucial to developing new treatments for patients with cancer. In this review, focusing on the anti-tumour T-cell response, we summarize our understanding of how tumours, cancer treatments and the immune system interact, how tumours evade the immune response and how this process could be manipulated for the benefit of patients with cancer. © 2010 Macmillan Publishers Limited All rights reserved.

Meniawy T.M.,University of Western Australia | Meniawy T.M.,National Center for Asbestos Related Disease | Creaney J.,University of Western Australia | Creaney J.,National Center for Asbestos Related Disease | And 4 more authors.
British Journal of Cancer | Year: 2013

Background:Recent studies proposed neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in malignant pleural mesothelioma (MPM). We examined baseline prognostic variables including NLR and the EORTC and CALGB models as predictors of overall survival (OS) in MPM.Methods:In this retrospective study, 274 consecutive eligible, newly presenting patients with MPM were included. Of these, 159 received chemotherapy, 10 had tri-modality therapy, 2 underwent surgery only and 103 received supportive care alone. Univariate analyses and multivariate Cox models were calculated for OS.Results:In univariate analysis, poor prognostic factors were: age ≥65 years, nonepithelioid histology, stage III-IV, poor performance status (PS), weight loss, chest pain, low haemoglobin and high platelet count. A baseline NLR≥5 did not predict worse OS (hazard ratio (HR) 1.25; P=0.122). On multivariate analysis, age, histology, PS, weight loss, chest pain and platelet count remained significant. The EORTC and CALGB prognostic groups were validated as predictive for OS (HR 1.62; P<0.001 and HR 1.65; P<0.001, respectively).Conclusion:Our findings validate standard prognostic variables and the existing EORTC and CALGB models, but not NLR, at initial diagnosis of MPM. In guiding patient management at diagnosis, it is important to consider multiple baseline variables that jointly predict survival. © 2013 Cancer Research UK.

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