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 decision-making.

Highlights

  • We systematically assessed the prognostic and predictive value of infiltrating adaptive and innate immune cells in a large cohort of patients with advanced mesothelioma

  • 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

  • Mesothelioma incidence is predicted to peak in the United Kingdom in 2020

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Summary

Methods

A tissue microarray from 302 samples was constructed. Markers of adaptive immune response in T-cells (CD8 þ , FOXP3 þ , CD4 þ , CD45RO þ , CD3 þ ) and B-cells (CD20 þ ), and of innate immune response; neutrophils (NP57 þ ), natural killer cells (CD56 þ ) and macrophages (CD68 þ ) were evaluated. Patients included in the cohort had a pathological diagnosis of mesothelioma dated at least 2 years prior to analysis. A tissue microarray (TMA) was generated from this cohort. Some cases could not be evaluated as there was tissue loss in the formation of the TMA. Cases were included in the analysis if at least three high-powered fields were available. A subcohort of B170 cases was evaluated for CD3 þ

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