The purpose of this study was to investigate immunological effector cells and angiogenesis in malignant pleural mesothelioma (MPM) patients, who underwent multimodality treatments. Clinical and pathological characteristics of 57 patients, with International Mesothelioma Interest Group stage II-III MPM, who underwent two different multimodality treatments (with and without immunotherapy) between 1999 and 2008 were analyzed. CD8+, CD4+ and Foxp3+ tumor-infiltrating lymphocytes, tryptase and chymase mast cells (MCs), CD34, number of microvessels and vascular endothelial growth factor were determined by immunohistochemistry. The histology was 51 epitheliomorf and 6 biphasic. The stage was III in 41 cases and II in 16 cases. With an average follow-up of 69 months (range 9-115) 14 patients are still alive and the overall median actuarial survival is 21.4 months. Tryptase MCs, CD8+ and Foxp3+ lymphocytes had significantly increased in the interleukin 2 (IL-2) treated group. Moreover, the number of microvessels was significantly lower in IL-2 treated patients. This study indicates that immunotherapy leads to an increase in cytotoxic CD8+ lymphocytes and tryptase MCs and to a decrease of the tumoral neoangiogenesis. Changes in MPM microenvironment induced by immunotherapy may play a major role in the local control of this disease and need further investigations.