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Patho- and immunobiology of malignant mesothelioma: characterisation of tumour infiltrating leucocytes and cytokine production in a murine model

  • Original Articles
  • Malignant Mesothelioma, TIL, CD3, TGFβ, Interleukin-6
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Abstract

Malignant mesothelioma (MM) is an aggressive, uniformly fatal serosal tumour, usually associated with asbestos exposure, for which there currently is no effective treatment. In order to gain insight into the mechanism(s) whereby MM might escape immune surveillance, a murine model for MM was used (a) to characterise the tumour-infiltrating lymphocytes (TIL) and macrophages (TIM) phenotypically, (b) to examine systemic immune recognition of MM, and (c) to examine the possible influence of tumour-derived cytokines on systemic and local pathobiological manifestations of MM. A profound down-regulation of lymphocyte surface markers, known to be infolved in T cell activation, was found in TIL. Likewise, although TIM were present in large numbers, their expression of MHC class II antigen and integrins was weak or absent, suggestive of altered functional activity. Significant amounts of cytokines, in particular transforming growth factor β, interleukin-6 (IL-6), IL-1 and tumour necrosis factor were produced during the course of MM tumour development-directly by the MM cells and/or indirectly in response to tumour growth. These factors may contribute both to derangement of antitumour effector mechanisms and to the clinical and pathological manifestations of the disease.

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Author notes

  1. D. R. Fitzpatrick

    Present address: Transplantation Biology Unit, Queensland Institute of Medical Research, Herston, Queensland

  2. M. R. Davis

    Present address: Department of Neuropathology, Royal Perth Hospital, Perth, W.A.

  3. L. S. Manning

    Present address: Cell Biology Research Unit, Fremantle Hospital, Fremantle, W.A.

Authors and Affiliations

  1. QEII Medical Centre, University of Western Australia Department of Medicine, Nedlands, Western Australia

    H. Bielefeldt-Ohmann, D. R. Fitzpatrick, A. L. Marzo, A. G. Jarnicki, R. P. Himbeck, M. R. Davis, L. S. Manning & B. W. S. Robinson

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  1. H. Bielefeldt-Ohmann
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Bielefeldt-Ohmann, H., Fitzpatrick, D.R., Marzo, A.L. et al. Patho- and immunobiology of malignant mesothelioma: characterisation of tumour infiltrating leucocytes and cytokine production in a murine model. Cancer Immunol Immunother 39, 347–359 (1994). https://doi.org/10.1007/BF01534421

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  • DOI: https://doi.org/10.1007/BF01534421

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