Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma.

Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combined analysis of T cell clustering with T cell receptor (TCR) clone expansion shows that potential tumor-killing T cells are mainly categorized into pre-exhausted/exhausted and effector CD8 T subsets, as well as cytotoxic CD4 T subsets.

SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation.

Germinal center (GC) responses potentiate the generation of follicular regulatory T (T) cells. However, the molecular cues driving T cell formation remain unknown. Here, we show that sclerostin domain-containing protein 1 (SOSTDC1), secreted by a subpopulation of follicular helper T (T) cells and T-B cell border-enriched fibroblastic reticular cells, is developmentally required for T cell generation.