Spatial proximity between T and PD-L1 expressing cells as a prognostic biomarker for oropharyngeal squamous cell carcinoma

Anna Maria Tsakiroglou, Martin Fergie, Ken Oguejiofor, Kim Linton, David Thomson, Peter L Stern, Susan Astley, Richard Byers, Catharine M L West

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Fulfilling the promise of cancer immunotherapy requires novel predictive biomarkers to characterise the host immune microenvironment. Deciphering the complexity of immune cell interactions requires an automated multiplex approach to histological analysis of tumour sections. We tested a new automatic approach to select tissue and quantify the frequencies of cell-cell spatial interactions occurring in the PD1/PD-L1 pathway, hypothesised to reflect immune escape in oropharyngeal squamous cell carcinoma (OPSCC).

METHODS: Single sections of diagnostic biopsies from 72 OPSCC patients were stained using multiplex immunofluorescence (CD8, PD1, PD-L1, CD68). Following multispectral scanning and automated regions-of-interest selection, the Hypothesised Interaction Distribution (HID) method quantified spatial proximity between cells. Method applicability was tested by investigating the prognostic significance of co-localised cells (within 30 μm) in patients stratified by HPV status.

RESULTS: High frequencies of proximal CD8+ and PD-L1+ (HR 2.95, p = 0.025) and PD1+ and PD-L1+ (HR 2.64, p = 0.042) cells were prognostic for poor overall survival in patients with HPV negative OPSCC (n = 31).

CONCLUSION: The HID method can quantify spatial interactions considered to reflect immune escape and generate prognostic information in OPSCC. The new automated approach is ready to test in additional cohorts and its applicability should be explored in research and clinical studies.

Original languageEnglish
Pages (from-to)539–544
JournalBritish Journal of Cancer
Early online date6 Dec 2019
Publication statusPublished - 6 Dec 2019

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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