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Combining measures of immune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Montfort, Anne 
Barker-Clarke, Rowan J 
Piskorz, Anna M 
Supernat, Anna 
Moore, Luiza 

Abstract

BACKGROUND: In colorectal and breast cancer, the density and localisation of immune infiltrates provides strong prognostic information. We asked whether similar automated quantitation and combined analysis of immune infiltrates could refine prognostic information in high-grade serous ovarian carcinoma (HGSOC) and tested associations between patterns of immune response and genomic driver alterations. METHODS: Epithelium and stroma were semi-automatically segmented and the infiltration of CD45RO+, CD8+ and CD68+ cells was automatically quantified from images of 332 HGSOC patient tissue microarray cores. RESULTS: Epithelial CD8 [p = 0.027, hazard ratio (HR) = 0.83], stromal CD68 (p = 3 × 10-4, HR = 0.44) and stromal CD45RO (p = 7 × 10-4, HR = 0.76) were positively associated with survival and remained so when averaged across the tumour and stromal compartments. Using principal component analysis, we identified optimised multiparameter survival models combining information from all immune markers (p = 0.016, HR = 0.88). There was no significant association between PTEN expression, type of TP53 mutation or presence of BRCA1/BRCA2 mutations and immune infiltrate densities or principal components. CONCLUSIONS: Combining measures of immune infiltration provided improved survival modelling and evidence for the multiple effects of different immune factors on survival. The presence of stromal CD68+ and CD45RO+ populations was associated with survival, underscoring the benefits evaluating stromal immune populations may bring for prognostic immunoscores in HGSOC.

Description

Keywords

Cystadenocarcinoma, Serous, Female, Humans, Lymphocytes, Tumor-Infiltrating, Ovarian Neoplasms, Prognosis, Tumor Microenvironment

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

122

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Cancer Research UK (CB4150)
Cancer Research UK (C14303/A17197)
Cancer Research UK (22905)
Cancer Research UK (A22905)
Cancer Research UK (A15973)
Cancer Research UK (A15601)
We acknowledge funding and support from Cancer Research UK (grant numbers A16354, A25714, A15973, A15601), ERC Advanced Grant ERC322566, the Universities of Queen Mary, National Institute for Health Research Cambridge, National Cancer Research Network, the Experimental Cancer Medicine Centres and Hutchison Whampoa Limited. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.