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Spatially Resolved and Quantitative Analysis of the Immunological Landscape in Human Meningiomas

Authors: Yeung, Jacky; Yaghoobi, Vesal; Aung, Thazin N.; Vesely, Matthew D.; Zhang, Tianxiang; Gaule, Patricia; Gunel, Murat; Rimm, David L.; Chen, Lieping

Online: https://academic.oup.com/jnen/article-abstract/80/2/150/6061497?redirectedFrom=fulltext

Issue: J Neuropathol Exp Neurol . 2021 Jan 20;80(2):150-159.


The immunological status of human meningiomas is not well understood, hindering the development of rational immunotherapeutic strategies. We measured the levels of PD-L1, PD-L2, and immune cell subsets using multiplex quantitative immunofluorescence in a tissue microarray composed of 73 human meningiomas (56 WHO Grade 1, 13 WHO Grade 2, and 4 WHO Grade 3). We analyzed tumor-infiltrating immune cell populations, T-cell activation/dysfunction, and macrophage phenotypes. PD-L1 and PD-L2 were detected in 5.8% and 68.7% of cases, respectively. There was a higher PD-L1 expression in CD68+ macrophages compared with tumor cells (p < 0.001). There was a weak positive correlation between PD-L1 expression and CD3+ T-cell infiltration. The level of CD3+ cells and T-cell activation/proliferation in human meningiomas were highly variable with an increased CD4-to-CD8 ratio in higher grade tumors (p < 0.05). There was a stronger correlation between GZMB/Ki67 with PD-L2 than PD-L1. We found that 15.23%, 6.66%, and 5.49% of macrophages were CD163+, CD68+, and CD163+CD68+, respectively. In cases where there is high CD3+ T-cell infiltration, 23.5% and 76.5% had dormant and activated T-cell phenotypes, respectively. We conclude that human meningiomas are either PD-L1low TILlow or PD-L1low TILhigh tumors and harbor variable TIL infiltration and phenotypes.