期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.850226
关键词
T cells; chemokine receptors; integrins; chemokines; glioblastoma; migration; scRNA-seq
类别
资金
- Neurosurgical Research Foundation
- Hospital Research Foundation Group
- Tour de Cure Senior Research
- Cancer Council SA Beat Cancer Project
- Royal Adelaide Hospital Research Fund
- Health Services Charitable Gifts Board (Adelaide)
- Cure Brain Cancer Foundation Infrastructure Grant
- National Health and Medical Research Council of Australia [1156693]
- Australian Research Council [FT16010036]
- University of Adelaide Honours Scholarship
- National Health and Medical Research Council of Australia [1156693] Funding Source: NHMRC
This study characterized the chemokine receptor and integrin expression profiles of endogenous glioblastoma-infiltrating T cells and identified potential homing receptor-ligand pairs that could enhance the tumour-homing properties of future T-cell immunotherapies for glioblastoma.
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.
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