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

被引:16
|
作者
Kollis, Paris M. M. [1 ,2 ]
Ebert, Lisa M. M. [1 ,2 ,3 ]
Toubia, John [4 ]
Bastow, Cameron R. R. [5 ]
Ormsby, Rebecca J. J. [6 ]
Poonnoose, Santosh I. I. [6 ,7 ]
Lenin, Sakthi [8 ]
Tea, Melinda N. N. [8 ]
Pitson, Stuart M. M. [2 ,8 ]
Gomez, Guillermo A. A. [9 ]
Brown, Michael P. P. [1 ,2 ,3 ]
Gargett, Tessa [1 ,2 ,3 ]
机构
[1] SA Pathol & Univ South Australia, Ctr Canc Biol, Translat Oncol Lab, Adelaide, SA, Australia
[2] Univ Adelaide, Fac Hlth & Med Sci, Adelaide Med Sch, Adelaide, SA, Australia
[3] Royal Adelaide Hosp, Canc Clin Trials Unit, Adelaide, SA, Australia
[4] SA Pathol & Univ South Australia, Ctr Canc Biol, Australian Canc Res Fdn ACRF, Canc Genom Facil, Adelaide, SA, Australia
[5] Univ Adelaide, Chemokine Biol Lab, Mol Life Sci, Adelaide, SA, Australia
[6] Flinders Univ S Australia, Flinders Hlth & Med Res Inst, Coll Med & Publ Hlth, Adelaide, SA, Australia
[7] Flinders Med Ctr, Dept Neurosurg, Adelaide, SA, Australia
[8] SA Pathol & Univ South Australia, Ctr Canc Biol, Mol Therapeut Lab, Adelaide, SA, Australia
[9] SA Pathol & Univ SouthAustralia, Ctr Canc Biol, Tissue Architecture & Organ Funct Lab, Adelaide, SA, Australia
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
基金
澳大利亚研究理事会; 英国医学研究理事会;
关键词
T cells; chemokine receptors; integrins; chemokines; glioblastoma; migration; scRNA-seq; CXC CHEMOKINE; EXPRESSION; GLIOMA; TRAFFICKING; SURVIVAL; BRAIN; CNS; INFLAMMATION; ABSENCE; GROWTH;
D O I
10.3389/fimmu.2022.850226
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页数:19
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