IL-6 underlies microenvironment immunosuppression and resistance to therapy in glioblastoma

The glioblastoma tumor immune microenvironment (TIME) is an immunosuppressive barrier to therapy that encumbers glioblastoma responses to immune checkpoint inhibition (ICI). Immunosuppressive cytokines, pro-tumor macrophages and myeloid cells, and exhausted T-cells are hallmarks of the glioblastoma TIME. Here we integrate spatial and single-cell analyses of patient-matched human glioblastoma samples before and after ICI with genetic, immunologic, single-cell, and therapeutic studies in preclinical models to show that interleukin-6 (IL-6) neutralization reprograms the glioblastoma TIME to sensitize mouse glioblastoma allografts to ICI and ICI plus radiotherapy. We find rare human glioblastomas that achieve clinical responses to ICI have lower pre-treatment IL-6 compared to glioblastomas that do not respond to ICI. We show that diverse immunostimulatory gene therapies suppress IL-6 in mouse glioblastoma allografts, and that IL-6 from multiple cell types the TIME reduces survival in precli..., , , # IL-6 underlies microenvironment immunosuppression and resistance to therapy in glioblastoma

[https://doi.org/10.5061/dryad.c59zw3rkm](https://doi.org/10.5061/dryad.c59zw3rkm)

## Description of the data and file structure

Mass cytometry data for referenced manuscript

### Files and variables

#### File: Fig4c_d_tumor.csv

**Description:** Input cell frequency data for PCA

Variables: 

* filename: individual samples included in analysis, including GL261 mouse tumor GFP and untreated (unt) controls, SB28 GFP and untreated (unt) controls, and gbm human glioblastoma samples. Numbers following the sample designation indicate unique identifying mouse or human tumor sample number. 
* B cells total: total B cell frequency
* CD4.conv: conventional CD4+ T cells frequency
* CD8: total CD8+ T cells frequency
* cDC1: conventional dendritic cells 1 frequency
* cDC2: conventional dendritic cells 2 frequency
* gd T: gamma delta T cells frequency
* Microglia: Microglia frequency
* mono/mac: monocyt..., ,