Profiling of Tumour-Infiltrating Lymphocytes and Tumour-Associated Macrophages in Ovarian Epithelial Cancer—Relation to Tumour Characteristics and Impact on Prognosis

Author:

Stout Annabel1,Facey Natalya2,Bhatnagar Anjali3,Rice Kirstie3,Berditchevski Fedor4ORCID,Kearns Daniel2ORCID,Metcalf Amy5,Elghobashy Alaa6ORCID,Shaaban Abeer M.2ORCID

Affiliation:

1. Department of Gynaecological Oncology, Birmingham Women’s Hospital, Edgbaston, Birmingham B15 2TG, UK

2. Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham B15 2GW, UK

3. Department of Cellular Pathology, The Royal Wolverhampton NHS Trust, New Cross Hospital, Wolverhampton WV10 0QP, UK

4. Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

5. Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK

6. Department of Gynaecological Oncology, The Royal Wolverhampton NHS Trust, New Cross Hospital, Wolverhampton WV10 0QP, UK

Abstract

Early evidence suggests a strong impact of tumour-infiltrating lymphocytes (TILs) on both the prognosis and clinical behaviour of ovarian cancer. Proven associations, however, have not yet translated to successful immunotherapies and further work in the field is urgently needed. We aimed to analyse the tumour microenvironment of a well-characterised cohort of ovarian cancer samples. Tumour markers were selected owing to their comparative underrepresentation in the current literature. Paraffin-embedded, formalin-fixed tumour tissue blocks of 138 patients representative of the population and including early stage disease were identified, stained for CD3, CD20, CD68 and CD163 and analysed for both the stromal and intertumoral components. Data were statistically analysed in relation to clinical details, histological subtype, borderline vs. malignant status, survival and management received. Mean stromal CD3, total CD3 count, mean stromal CD20 and total CD20 count all correlated negatively with survival. Malignant ovarian tumours consistently demonstrated significantly higher infiltration of all analysed immune cells than borderline tumours. Assessment of the stromal compartment produced a considerably higher proportion of significant results when compared to the intra-tumoural infiltrates. Customary assessment of solely intra-tumoural cells in advanced stage disease patients undergoing primary debulking surgery should be challenged, with recommendations for future scoring systems provided.

Funder

Birmingham Cancer Research UK Centre

Publisher

MDPI AG

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