In multiple tumor types, prediction of response to immune therapies relates to the presence, distribution and activation state of tumor infltrating lymphocytes (TILs). Although such therapies are, to date, unsuccessful in gliomas, little is known on the immune contexture of TILs in these tumors. We assessed whether low and high-grade glioma (LGG and HGG, grade II and IV respectively) difer with respect to number, location and tumor reactivity of TILs; as well as expression of molecules involved in the trafcking and activation of T cells. Intra-tumoral CD8 T cells were quantifed by fow cytometry (LGG: n=12; HGG: n=8) and immunofuorescence (LGG: n=28; HGG: n=28). Neoantigen load and expression of Cancer Germline Antigens (CGAs) were assessed using whole exome sequencing and RNA-seq. TIL-derived DNA was sequenced and the variable domain of the TCRβ chain was classifed according to IMGT nomenclature. QPCR was used to determine expression of T cell-related genes. CD8 T cell numbers were signifcantly lower in LGG and, in contrast to HGG, mainly remained in close vicinity to blood vessels. This was accompanied by lower expression of chemo-attractants CXCL9, CXCL10 and adhesion molecule ICAM1. We did not observe a diference in the number of expressed neoantigens or CGAs, nor in diversity of TCR-Vβ gene usage. In summary, LGG have lower numbers of intra-tumoral CD8 T cells compared to HGG, potentially linked to decreased T cell trafcking. We have found no evidence for distinct tumor reactivity of T cells in either tumor type. The near absence of TILs in LGG suggest that, at present, checkpoint inhibitors are unlikely to have clinical efcacy in this tumor type.,
Scientific Reports
Department of Neurology

Weenink, B., Draaisma, K., Ooi, H.Z., Kros, J., Smitt, P., Debets, R., & French, P. (2019). Low-grade glioma harbors few CD8 T cells, which is accompanied by decreased expression of chemo-attractants, not immunogenic antigens. Scientific Reports, 9. doi:10.1038/s41598-019-51063-6