Vasquez JC, Huttner A, Zhang L, Marks A, Chan A, Baehring
JM, Kahle KT, Dhodapkar KM. SOX2 immunity and tissue resident memory in
children and young adults with glioma. J Neurooncol. 2017 Jun 15. doi:
10.1007/s11060-017-2515-8. [Epub ahead of print]
Abstract
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.
Courtesy of: https://www.mdlinx.com/neurology/medical-news-article/2017/07/06/glioma/7230213/?category=latest&page_id=1
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