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. 2017 Oct 24;117(9):1341-1348.
doi: 10.1038/bjc.2017.269. Epub 2017 Aug 17.

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

Serena J Chee  1   2 , Maria Lopez  1   3 , Toby Mellows  3   4 , Sharmali Gankande  3 , Karwan A Moutasim  1   3 , Scott Harris  5 , James Clarke  1 , Pandurangan Vijayanand  4 , Gareth J Thomas  1   6 , Christian H Ottensmeier  1   2   6
Affiliations

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

Serena J Chee et al. Br J Cancer. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative low and high T-cell densities (× 400) magnification: CD4+ and CD8+ cells.
Figure 2
Figure 2
Kaplan–Meier survival curves of adaptive immune markers associated with survival in epithelioid mesothelioma. (A) Kaplan–Meier curves for epithelioid mesothelioma survival according to CD4+ T-cell counts (log-rank test, P=0.005). (B) Kaplan–Meier curves for epithelioid mesothelioma survival according to FOXP3+ T-regulatory cell counts (log-rank test, P=0.024). (C) Kaplan–Meier curves for epithelioid mesothelioma survival according to CD20+ B-cell counts (log-rank test, P=0.008).
Figure 3
Figure 3
Kaplan–Meier survival curves of adaptive immune markers associated with survival in non-epithelioid mesothelioma. (A) Kaplan–Meier curves for non-epithelioid mesothelioma survival according to CD8+ T-cell counts (log-rank test, P=0.019). (B) Kaplan–Meier curves for non-epithelioid mesothelioma survival according to FOXP3+ T-regulatory cell counts (log-rank test, P=0.012).
See this image and copyright information in PMC

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