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

Our plain-English summary of Evaluating the effect of immune cells on the outcome of patients with mesothelioma, by S.J. Chee, M. Lopez, T. Mellows, et al (British Journal of Cancer, 2017).

The study

• Authors: S.J. Chee, M. Lopez, T. Mellows, S. Gankande, K.A. Moutasim, S. Harris, J. Clarke, P. Vijayanand, G.J. Thomas, C.H. Ottensmeier
• Journal: British Journal of Cancer
• Published: 2017;117(9):1341-1348
• Cited by: 59 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This study looked at immune cells inside mesothelioma tumours and whether their numbers were linked to how long patients lived. It did not study asbestos exposure. The authors stained archived tumour samples from 302 patients at a UK centre. The tissue was stored between 2004 and 2012 and taken before any systemic treatment. They counted several kinds of immune cells and analysed epithelioid tumours separately from non-epithelioid (biphasic and sarcomatoid) tumours. Median survival was 342 days (95% confidence interval 277 to 406 days) for epithelioid and 205 days (146 to 260 days) for non-epithelioid mesothelioma. In epithelioid tumours, high counts of CD4 and CD20 cells and low counts of FOXP3, CD68 and NP57 cells were associated with longer survival. In non-epithelioid tumours, low CD8 and low FOXP3 counts were. In a combined (multivariate) analysis, low FOXP3 remained associated with survival in both groups. High CD4, high CD20 and low NP57 also remained associated in epithelioid tumours. The authors concluded that immune cell patterns were linked to survival and differed between subtypes. They noted that small tissue samples may not represent the whole tumour.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of archived tumour tissue: a tissue microarray stained for immune cell markers, with the counts compared against patient survival
• Who was studied: 302 patients with mesothelioma from one large UK centre (Southampton), with tissue archived 2004 to 2012. Median age was 72 and 81% were men. Tumours were 172 epithelioid, 82 biphasic, 41 sarcomatoid and 7 undefined. 259 (86%) had thoracoscopy and pleural biopsy followed by talc pleurodesis, and 36 (12%) had radical surgery.
• Exposure: Asbestos exposure was not studied. The study measured immune cells in tumour tissue: several types of T-cells and B-cells, neutrophils, natural killer cells and macrophages. Counts were split into high and low at the average count for each marker.
• Main results:
  • In this cohort, median overall survival for epithelioid mesothelioma was 342 days (11.4 months, 95% CI 277 to 406 days).
  • In this cohort, median overall survival for non-epithelioid mesothelioma was 205 days (6.8 months, 95% CI 146 to 260 days).
  • In the epithelioid group, high CD4 (P = 0.005), low FOXP3 (P = 0.024) and high CD20 (P = 0.008) counts were associated with longer overall survival, by 7, 3 and 7 months respectively. CD8 counts were not associated with survival in this group (P = 0.983).
  • In the non-epithelioid group, low CD8 (P = 0.019) and low FOXP3 (P = 0.012) counts were each associated with a 4-month longer overall survival.
  • Among innate immune cells in the epithelioid group, low CD68 (macrophage) and low NP57 (neutrophil) counts were each associated with a 3-month longer overall survival. In the non-epithelioid group, no innate immune marker was significantly associated with survival.
  • In multivariate analysis of the epithelioid group, high CD4 (P = 0.003), high CD20 (P = 0.010), low FOXP3 (P = 0.000414) and low NP57 (P = 0.038) remained significantly associated with survival. In the non-epithelioid group, only low FOXP3 did (P = 0.043).
  • A CD4-to-CD8 ratio greater than 1 was associated with longer survival only in the epithelioid group (99 low, 59 high, 158 total; P = 0.047).
  • Of 166 patients with treatment data, 61 received chemotherapy. Among these 61 patients, a high CD4 count identified those who lived longer (P = 0.034); no effect was seen for CD8 cells.
  • WT1 expression was not associated with survival in either the epithelioid or the non-epithelioid group.
• The authors' conclusion: The authors concluded that, in mesothelioma treated with palliative intent, certain immune cell counts were associated with survival. They found that these associations differed between epithelioid and non-epithelioid tumours.
• Limitations the authors state:
  • Staining was done on small biopsy samples in the tissue microarray, which may not represent the whole tumour. This matters because mesothelioma has been shown to be polyclonal (made up of several cell lines) in origin.
  • The better survival of chemotherapy-treated patients was likely to reflect both which patients were selected for treatment and the effect of the treatment.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Macrophage, Epithelioid, Non-epithelioid, Multivariate Analysis, Histology.

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