ArticleCancer immunology, immunotherapy : CII2021
Immune infiltrate diversity confers a good prognosis in follicular lymphoma.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review.International journal of molecular sciences · 2024Pooled it
- Topological importance of CD8Annals of hematology · 2025Article
- Impact of positive CD4 cells on event-free survival in follicular lymphoma patients.Cancer medicine · 2024Article
- Article
- Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program.The American journal of pathology · 2024Article
- Long-term follow-up confirms the favourable prognostic impact of high numbers of tumour infiltrating CD3 T-cells in follicular lymphoma patients treated by rituximab-maintenance regimen.British journal of haematology · 2023Article
- Follicular Lymphoma Microenvironment Traits Associated with Event-Free Survival.International journal of molecular sciences · 2023Article
- High inter-follicular spatial co-localization of CD8+FOXP3+ with CD4+CD8+ cells predicts favorable outcome in follicular lymphoma.Hematological oncology · 2022Article
- Tumor Microenvironment and Microvascular Density in Follicular Lymphoma.Journal of clinical medicine · 2022Article
- Role and Mechanisms of Tumor-Associated Macrophages in Hematological Malignancies.Frontiers in oncology · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFollicular 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.
methodsDiagnostic 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).
resultsIncreased 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.
conclusionMultiplex 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.
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