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Open Access 01-12-2021 | Lymphoma | Original Article

Immune infiltrate diversity confers a good prognosis in follicular lymphoma

Authors: Anna-Maria Tsakiroglou, Susan Astley, Manàs Dave, Martin Fergie, Elaine Harkness, Adeline Rosenberg, Matthew Sperrin, Catharine West, Richard Byers, Kim Linton

Published in: Cancer Immunology, Immunotherapy | Issue 12/2021

Abstract

Background

Follicular lymphoma (FL) prognosis is influenced by the composition of the tumour microenvironment. We tested an automated approach to quantitatively assess the phenotypic and spatial immune infiltrate diversity as a prognostic biomarker for FL patients.

Methods

Diagnostic biopsies were collected from 127 FL patients initially treated with rituximab-based therapy (52%), radiotherapy (28%), or active surveillance (20%). Tissue microarrays were constructed and stained using multiplex immunofluorescence (CD4, CD8, FOXP3, CD21, PD-1, CD68, and DAPI). Subsequently, sections underwent automated cell scoring and analysis of spatial interactions, defined as cells co-occurring within 30 μm. Shannon’s entropy, a metric describing species biodiversity in ecological habitats, was applied to quantify immune infiltrate diversity of cell types and spatial interactions. Immune infiltrate diversity indices were tested in multivariable Cox regression and Kaplan–Meier analysis for overall (OS) and progression-free survival (PFS).

Results

Increased diversity of cell types (HR = 0.19 95% CI 0.06–0.65, p = 0.008) and cell spatial interactions (HR = 0.39, 95% CI 0.20–0.75, p = 0.005) was associated with favourable OS, independent of the Follicular Lymphoma International Prognostic Index. In the rituximab-treated subset, the favourable trend between diversity and PFS did not reach statistical significance.

Conclusion

Multiplex immunofluorescence and Shannon’s entropy can objectively quantify immune infiltrate diversity and generate prognostic information in FL. This automated approach warrants validation in additional FL cohorts, and its applicability as a pre-treatment biomarker to identify high-risk patients should be further explored. The multiplex image dataset generated by this study is shared publicly to encourage further research on the FL microenvironment.

Available only for authorised users

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Title: Immune infiltrate diversity confers a good prognosis in follicular lymphoma
Authors: Anna-Maria Tsakiroglou
Susan Astley
Manàs Dave
Martin Fergie
Elaine Harkness
Adeline Rosenberg
Matthew Sperrin
Catharine West
Richard Byers
Kim Linton
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keywords: Lymphoma
Rituximab
Rituximab
Published in: Cancer Immunology, Immunotherapy / Issue 12/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02945-0

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