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

Date

2022

Authors

Kollis, P.M.
Ebert, L.M.
Toubia, J.
Bastow, C.R.
Ormsby, R.J.
Poonnoose, S.I.
Lenin, S.
Tea, M.N.
Pitson, S.M.
Gomez, G.A.

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Journal article

Citation

Frontiers in Immunology, 2022; 13:850226-1-850226-19

Statement of Responsibility

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, and Tessa Gargett

Conference Name

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-cellbased 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 Tcell 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 glioblastomainfiltrating 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.

School/Discipline

Dissertation Note

Provenance

Description

Access Status

Rights

Copyright © 2022 Kollis, Ebert, Toubia, Bastow, Ormsby, Poonnoose, Lenin, Tea, Pitson, Gomez, Brown and Gargett. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

License

Call number

Persistent link to this record