TY - JOUR
T1 - Multi-scale spatial modeling of immune cell distributions enables survival prediction in primary central nervous system lymphoma
AU - Roemer, Margaretha G. M.
AU - van de Brug, Tim
AU - Bosch, Erik
AU - Berry, Daniella
AU - Hijmering, Nathalie
AU - Stathi, Phylicia
AU - Weijers, Karin
AU - Doorduijn, Jeannette
AU - Bromberg, Jacoline
AU - van de Wiel, Mark
AU - Ylstra, Bauke
AU - de Jong, Daphne
AU - Kim, Yongsoo
N1 - 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. 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. Publisher Copyright: © 2023 The Authors
PY - 2023/8/18
Y1 - 2023/8/18
N2 - 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.
AB - 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.
KW - Cell biology
KW - Computational bioinformatics
KW - Mathematical biosciences
KW - Neuroscience
KW - Oncology
UR - http://www.scopus.com/inward/record.url?scp=85165559326&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.isci.2023.107331
DO - https://doi.org/10.1016/j.isci.2023.107331
M3 - Article
C2 - 37539043
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 8
M1 - 107331
ER -