Single-cell RNA sequencing reveals heterogeneous immune landscape of tumor-infiltrating lymphocytes in the glioblastoma tumor microenvironment in the absence of IFNAR

Abstract

Abstract Glioblastoma (GBM) is known to be the most common malignant brain cancer with a very poor prognosis. Despite standard conventional therapies patient survival rates still remain poor and reasons for this may be due to the extensive tumor cellular heterogeneity of the tumor microenvironment. Type I interferons (IFNs) are a family of cytokines produced by multiple cell types and are known to play a role in anticancer immunity through their signaling via the interferon alpha receptor (IFNAR). We find that absence of IFNAR compromises anti-tumor immunity against GBM. Single-cell RNA analysis of the immune landscape of GBM tumor-bearing IfnαR−/−mice reveals that there is an overall decrease in tumor-infiltrating lymphocytes into the brain along with overall decreased expression of IFNγ, TNFα, and Granzyme A. Analysis of lymphoid cells including T cells and NK cells shows substantial decreased infiltration in the presence of GBM in IFNαR deficient mice. Notably, CD4 and CD8 T cell infiltration is considerably reduced, although how the functions of these cells are affected is yet unknown. Analysis of tumor-infiltrating myeloid cells in the absence of interferon signaling reveals decreased infiltration of monocytes and tumor-associated macrophages as well. Thus, in this study, we are able to see that the absence of type I interferon signaling affects the overall recruitment of lymphoid and myeloid cells during the progression of GBM and likely contributes to the exacerbation of anti-tumor immunity.