Abstract
Purpose
To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures.
Methods
The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications.
Results
The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (p = 0.019), and T8 dominant group than T4 dominant group (p = 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps.
Conclusions
Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.
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Data availability
All data are published within this paper and within accompanying supporting files (indicated in text) and accessed via weblink on the journal site.
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Acknowledgements
We thank Hye Jung Hong, R.N. for her support in collecting clinical data and laboratory management in contribution to this study.
Funding
This work was supported by the following funding sources: a National Research Foundation of Korea (NRF) grant funded by the Korea government Ministry of Science and ICT (MSIT) (NRF-2019R1A2C2005144 to C.-K.P.), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2020R1A2C2008949 to S.H.C.), the Creative-Pioneering Researchers Program through Seoul National University (SNU; to S.H.C.), and the Institute for Basic Science (IBS-R006-A1 to S.H.C.)
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ARK, KSC, MSK, SHC, E-CS and C-K.P wrote the manuscript. C.-KP, E-CS and SHC contributed to the conception and design of the project and revised the manuscript. SK, TC, HJY, and CEL collected tissue samples and performed the experiments. ARK and E-CS performed flow cytometric analysis. KSC and SHC performed the radiomics analysis. K-MK, HK, JHL, S-TL, JWK, Y-HK, and TMK contributed to the collection and analysis of clinical data. JKW and S-HP. performed histological diagnosis and molecular/genetic examinations. All authors participated in drafting and revising the article for important intellectual content and approved the final version for publication.
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This study involving human tissue and cells was approved by the Ethics Committee of the Seoul National University Hospital (IRB No. H-1902-062-1010).
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Kim, A.R., Choi, K.S., Kim, MS. et al. Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values. Cancer Immunol Immunother 70, 1995–2008 (2021). https://doi.org/10.1007/s00262-020-02836-w
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DOI: https://doi.org/10.1007/s00262-020-02836-w