Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma

Paris M. Kollis, Lisa M. Ebert, John Toubia, Cameron R. Bastow, Rebecca J. Ormsby, Santosh I. Poonnoose, Sakthi Lenin, Melinda N. Tea, Stuart M. Pitson, Guillermo A. Gomez, Michael P. Brown, Tessa Gargett

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
7 Downloads (Pure)

Abstract

Glioblastoma 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 prolonged the survival of patients with other cancers and have undergone early-phase clinical evaluation in glioblastoma patients. However, a major challenge for T-cell-based immunotherapy of glioblastoma and other solid cancers is T-cell infiltration into tumours. This process is mediated by chemokine-chemokine receptor and integrin-adhesion molecule interactions, yet the specific nature of the molecules that may facilitate T-cell homing into glioblastoma are unknown. Here, we have characterised chemokine receptor and integrin expression profiles of endogenous glioblastoma-infiltrating T cells, and the chemokine expression profile of glioblastoma-associated cells, by single-cell RNA-sequencing. Subsequently, chemokine receptors and integrins were validated at the protein level to reveal enrichment of receptors CCR2, CCR5, CXCR3, CXCR4, CXCR6, CD49a, and CD49d in glioblastoma-infiltrating T-cell populations relative to T cells in matched patient peripheral blood. Complementary chemokine ligand expression was then validated in glioblastoma biopsies and glioblastoma-derived primary cell cultures. Together, enriched expression of homing receptor-ligand pairs identified in this study implicate a potential role in mediating T-cell infiltration into glioblastoma. Importantly, our data characterising the migratory receptors on endogenous tumour-infiltrating T cells could be exploited to enhance the tumour-homing properties of future T-cell immunotherapies for glioblastoma.

Original languageEnglish
Article number850226
Number of pages19
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - Apr 2022

Keywords

  • chemokine receptors
  • chemokines
  • glioblastoma
  • integrins
  • migration
  • scRNA-seq
  • T cells

Fingerprint

Dive into the research topics of 'Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma'. Together they form a unique fingerprint.

Cite this