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

Abstract

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 decisionmaking.