Multi-scale spatial modeling of immune cell distributions enables survival prediction in primary central nervous system lymphoma

Margaretha G.M. Roemer, Tim van de Brug, Erik Bosch, Daniella Berry, Nathalie Hijmering, Phylicia Stathi, Karin Weijers, Jeannette Doorduijn, Jacoline Bromberg, Mark van de Wiel, Bauke Ylstra, Daphne de Jong*, Yongsoo Kim*

*Corresponding author for this work

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Abstract

To understand the clinical significance of the tumor microenvironment (TME), it is essential to study the interactions between malignant and non-malignant cells in clinical specimens. Here, we established a computational framework for a multiplex imaging system to comprehensively characterize spatial contexts of the TME at multiple scales, including close and long-distance spatial interactions between cell type pairs. We applied this framework to a total of 1,393 multiplex imaging data newly generated from 88 primary central nervous system lymphomas with complete follow-up data and identified significant prognostic subgroups mainly shaped by the spatial context. A supervised analysis confirmed a significant contribution of spatial context in predicting patient survival. In particular, we found an opposite prognostic value of macrophage infiltration depending on its proximity to specific cell types. Altogether, we provide a comprehensive framework to analyze spatial cellular interaction that can be broadly applied to other technologies and tumor contexts.

Original languageEnglish
Article number107331
JournaliScience
Volume26
Issue number8
DOIs
Publication statusPublished - 18 Aug 2023

Bibliographical note

Funding Information:
The project was supported by Dutch cancer society (KWF) grant KWF VU 2015-7925 and Leukemia Research Foundation, Hollis Brownstein Research grant. We acknowledge the Microscopy and Cytometry Core Facility at the Amsterdam UMC - location VUmc for providing assistance with the multiplex IHC / Vectra Polaris experiments and analyses. We also acknowledge the clinical co-principle investigator of the HOVON105/ALLG NHL 24 study Samar Issa (Department of Hematology, Middlemore Hospital, Auckland, New Zealand). We thank the collaborators at the HOVON Data Center, specifically Katerina Bakunina (HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands) for providing excellent clinical data and support. We also would like to acknowledge Eric J. Meershoek and Danielle Hoogmoed of Leica Biosystems, Amsterdam, the Netherlands, for their invaluable contribution to the development of the 9p24.1/PD-L1/PD-L2 FISH assay and support in obtaining FISH data for this study. Conceptulization, M.G.M.R. D.dJ. and Y.K.; Methodolgy, T.vdB. E.B. M.vdW. and Y.K.; Software, T.vdB. E.B. and Y.K.; Investigation, D.B. N.H. P.S. and M.G.M.R.; Data collection: D.B. N.H. P.S. K.W. M.G.M.R.; Clinical data collection: J.D. J.B.; Writing-Original Draft, M.G.M.R. B.Y. D.dJ. and Y.K.; Writing - Review & Editing, Y.K. and D.dJ.; Resources, K.W. J.D. J.B. B.Y.; Supervision, M.vdW. Y.K. and D.dJ. The authors have no conflicts of interest.

Publisher Copyright:
© 2023 The Authors

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