Evaluating the effect of immune cells on the outcome of patients with mesothelioma

Background: We systematically assessed the prognostic and predictive value of infiltrating adaptive and innate immune cells in a large cohort of patients with advanced mesothelioma. Methods: A tissue microarray from 302 samples was constructed. Markers of adaptive immune response in T-cells (CD8(+), FOXP3(+), CD4(+), CD45RO(+), CD3(+)) and B-cells (CD20(+)), and of innate immune response; neutrophils (NP57(+)), natural killer cells (CD56(+)) and macrophages (CD68(+)) were evaluated. Results: We found that in the epithelioid tumours, high CD4(+) and CD20(+) counts, and low FOXP3(+), CD68(+) and NP57(+) counts linked to better outcome. In the non-epithelioid group low CD8(+) and low FOXP3(+)counts were beneficial. On multivariate analysis low FOXP3(+) remained independently associated with survival in both groups. In the epithelioid group additionally high CD4(+), high CD20(+), and low NP57(+) counts were prognostic. Conclusions: Our data demonstrate for the first time, in predominately advanced disease, the association of key markers of adaptive and innate immunity with survival and the differential effect of histology. A better understanding of the immunological drivers of the different subtypes of mesothelioma will assist prognostication and disease-specific clinical decision-making.