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We tested an automated approach to quantitatively assess the phenotypic and spatial immune infiltrate diversity as a prognostic biomarker for FL patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>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\u00a0\u03bcm. Shannon\u2019s 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\u2013Meier analysis for overall (OS) and progression-free survival (PFS).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Increased diversity of cell types (HR\u2009=\u20090.19 95% CI 0.06\u20130.65, <jats:italic>p<\/jats:italic>\u2009=\u20090.008) and cell spatial interactions (HR\u2009=\u20090.39, 95% CI 0.20\u20130.75, <jats:italic>p<\/jats:italic>\u2009=\u20090.005) 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Multiplex immunofluorescence and Shannon\u2019s 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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00262-021-02945-0","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T10:03:00Z","timestamp":1619776980000},"page":"3573-3585","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immune infiltrate diversity confers a good prognosis in follicular lymphoma"],"prefix":"10.1007","volume":"70","author":[{"given":"Anna-Maria","family":"Tsakiroglou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Astley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man\u00e0s","family":"Dave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Fergie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Harkness","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Sperrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-0365","authenticated-orcid":false,"given":"Richard","family":"Byers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Linton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,30]]},"reference":[{"key":"2945_CR1","doi-asserted-by":"publisher","first-page":"2902","DOI":"10.1200\/JCO.2009.26.1693","volume":"28","author":"T Relander","year":"2010","unstructured":"Relander T, Johnson NA, Farinha P et al (2010) Prognostic factors in follicular lymphoma. 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