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

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.