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

We hypothesised that Treg cells preferentially expand/infiltrate inside murine mesotheliomas. Immunotherapy based on the manipulation of Treg cell populations should therefore be targeted to the tumour site. The AE17 murine mesothelioma model was used for this study. Both intra-tumoural Treg 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 Treg cells using the PC61 anti-CD25 mAb was then examined. We identified CD4+ Treg cells co-expressing both the CD25 cell surface marker and the transcription factor Foxp3 within murine mesotheliomas. These intra-tumoural Treg 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 Treg cells with anti-CD25 mAb injected directly into the tumours can cause significantly reduced tumour growth. Localised, intra-tumoural depletion of Treg cells is a new, clinically relevant treatment option for established tumours.