Therapies targeting immune checkpoints are effective in
tumors with a high mutation burden that express multiple neo-
antigens. However, glial
tumors including those seen in children carry fewer mutations and there is an unmet need to identify new antigenic targets of anti-
tumor immunity. SOX2 is an embryonal stem cell
antigen implicated in the biology of
glioma initiating cells. Expression of SOX2 by pediatric glial
tumors and the capacity of the immune system in these patients to recognize SOX2 has not been previously studied. We examined the expression of SOX2 on archived
paraffin-embedded tissue from pediatric glial
tumors. The presence of T-cell immunity to SOX2 was examined in both blood and
tumor-infiltrating T-cells in children and young adults with
glioma. The nature of
tumor-infiltrating immune cells was analyzed with a 37-marker panel using single-cell mass cytometry. SOX2 is expressed by
tumor cells but not surrounding normal tissue in pediatric
gliomas of all grades. T-cells against this
antigen can be detected in blood and
tumor tissue in
glioma patients. Glial
tumors are enriched for CD8/CD4 T-cells with tissue resident memory (TRM; CD45RO+, CD69+, CCR7-) phenotype, which co-express multiple inhibitory checkpoints including PD-1, PD-L1 and TIGIT.
Tumors also contain natural killer cells with reduced expression of lytic
granzyme. Our data demonstrate immunogenicity of SOX2, which is specifically overexpressed on pediatric glial
tumor cells. Harnessing
tumor immunity in
glioma will likely require the combined targeting of multiple inhibitory checkpoints.