PT  - JOURNAL ARTICLE
AU  - C. Jackaman
AU  - S. Cornwall
AU  - A. M. Lew
AU  - Y. Zhan
AU  - B. W. S. Robinson
AU  - D. J. Nelson
TI  - Local effector failure in mesothelioma is not mediated by CD4<sup>+</sup> CD25<sup>+</sup> T-regulator cells
AID  - 10.1183/09031936.00101008
DP  - 2009 Jul 01
TA  - European Respiratory Journal
PG  - 162--175
VI  - 34
IP  - 1
4099  - http://erj.ersjournals.com/content/34/1/162.short
4100  - http://erj.ersjournals.com/content/34/1/162.full
SO  - Eur Respir J2009 Jul 01; 34
AB  - The aim of the present study was to define the point at which mesothelioma T-cell responses fail in order to design better immunotherapies. A murine model of mesothelioma was used which was established with asbestos. Inoculation of tumour cells into syngeneic mice results in progressing tumours with similar histopathology to human mesothelioma. The tumour cells secrete a marker tumour antigen similar to secreted tumour-associated products, such as mesothelin. The mesothelioma microenvironment contains stromal elements including dendritic cells, effector CD8+ and CD4+ T-cells, and CD4+ T-regulatory (Tregs) cells, all of which are activated in situ, implying chronic inflammation. Tumour antigens are rapidly transported to draining lymph nodes wherein tumour-specific T-cell responses are generated. Despite the generation of potent CD8+ cytotoxic lymphocyte in lymphoid organs, those that infiltrate tumours cannot restrain tumour growth suggesting local suppression. Splenic Tregs did not suppress protective responses in adoptive transfer experiments suggesting that systemic Tregs play little role in regulating anti-mesothelioma immune responses. Finally, removal of CD25+ Tregs from the tumour site and lymphoid organs did not alter tumour growth with or without interleukin (IL)-2 or IL-21 immunotherapy. Tregs are not potent regulators of anti-mesothelioma immunity and targeting these cells may not improve results.