Intra-tumoural regulatory T cells: A potential new target in cancer immunotherapy

We hypothesised that T-reg cells preferentially expand/infiltrate inside murine mesotheliomas. Immunotherapy based on the manipulation of T-reg cell Populations should therefore be targeted to the tumour site. The AE17 murine mesothelioma model was used for this Study. Both intra-tumorral T-reg cells and those in the periphery of tumour-bearing mice were identified by flow cytometry. The effect on tumour growth of intra-tumoural depletion of T-reg Cells using the PC61 anti-CD25 mAb was then examined. We identified CD4(+) T-reg cells co-expressing both the CD25 cell surface marker and the transcription factor Foxp3 within murine mesotheliomas. These intratumoral T-reg cells increase significantly as a percentage of total CD4(+) T cells within the tumour as it grows. We showed that the depletion of intra-tumoural T-reg cells with anti-CD25 mAb injected directly into the tumours can cause significantly reduced tumour growth. Localised, intra-tumoural depletion of T-reg cells is a new, clinically relevant treatment option for established tumours. (c) 2006 Elsevier Inc. All rights reserved.