Asbestos is naturally occurring mineral fiber and one of representative harmful and tumorigenic materials. Occupational or environmental exposure to asbestos is still a global issue to cause asbestos-related diseases (ARD), in particular malignant mesothelioma is a serious disease with poor prognosis. It takes a long period of about 40 years to develop mesothelioma after inhalation exposure to asbestos, which is known to accumulate in regional lymph nodes. Those clues motivated us to examine immunological effects of asbestos exposure by cull culture experiments, omics data and broad analyses for peripheral blood of patients with mesothelioma. Our studies clarified several key events of asbestos-caused functional impairment in NK, helper T (Th) and cytotoxic T cells (CTL) as well as augmentation in regulatory T cells, associated with decrease in NKp46, IFN-gamma, CXCR3 and perforin and increase in CTLA-4, which were also observed in patients with malignant mesothelioma. In addition, it was also found that diffuse pleural thickening, a benign type of ARD, showed better characteristics of anti-tumor immunity compared with malignant mesothelioma, including high expression of perforin in CTL and low expression of GITR on cell surface of Treg. Those findings indicate that asbestos exposure has a potential to cause suppressed immune functions, which might contribute to the pathogenesis of malignant mesothelioma together with directly tumorigenic effect of asbestos on mesothelial cells. On the basis of our obtained knowledge, immunological scoring devices with mathematical formulae were also developed, in which M-score successfully distinguished patients with mesothelioma from other people. Moreover, our recent study about transcriptome of human cytotoxic T cell line demonstrated that continuous exposure to asbestos causes gradual decline in IFN-gamma expression and shared alteration in expression of transcripts among the types of asbestos fiber. All of our obtained findings together with more those in future will contribute to early diagnosis of and therapeutical strategy for mesothelioma in people exposed to asbestos.