ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Characterising T-cell migratory cues in glioblastoma lesions (#143)

Paris M Kollis 1 2 , Lisa M Ebert 1 2 , Tessa Gargett 1 2 , John Toubia 2 , Michael P Brown 1 2 3
  1. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
  2. Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia
  3. Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, SA, Australia

Glioblastoma (GBM) is the most common and aggressive form of primary brain cancer, with no improvements in the 5-year survival rate of 4.6% over the past three decades. T-cell-based immunotherapies such as immune-checkpoint inhibitors and chimeric antigen receptor T-cell therapy have had outstanding success as treatments for some cancers, and pose as new survival-prolonging treatments for GBM patients. Major challenges for T-cell-based immunotherapy of GBM and other solid cancers is T-cell infiltration into tumours, which is mediated by chemokine-chemokine receptor and integrin-adhesion molecule interactions. However, in GBM, the interactions that facilitate T-cell homing into tumours are unknown. Here, we have characterised the complete chemokine receptor and integrin expression profiles of endogenous GBM T-cells and chemokine expression profile of GBM-associated cells by single-cell RNA-sequencing. Subsequently, chemokine receptors and integrins were validated at the protein level to reveal enrichment of multiple migratory receptors in GBM-infiltrating T-cell populations relative to T-cells in matched patient peripheral blood. Complementary chemokine ligand expression was then investigated in GBM biopsies and GBM-derived primary cell-lines. Together, enriched expression of homing receptor-ligand pairings identified in this work implicate a role for these axes in mediating T-cell infiltration into GBM lesions. These findings may permit identification of migratory receptors that could be exploited to improve T-cell-based immunotherapy for GBM and possibly other solid tumours.