Dataset Information

PD-1+ and PD-1- CD4+ Teff and Treg cells in Glioblastoma and Health

ABSTRACT:

PD-1 is an important immune checkpoint inhibitor that shows great promise in the clinic, particularly for melanoma and lung cancers. Since PD-1 is also expressed on infiltrating CD4+ Treg and Teffector cells in glioblastoma, we sought to better understand the role of PD-1 on these infiltrating CD4+ Treg and Teffector cells. To this end, we performed functional and transcriptional profiling using CD4+ Treg and Teffector cells isolated from healthy donors and glioblastoma patients (from both tumors and blood).

PROVIDER: phs001079 | dbGaP |

SECONDARY ACCESSION(S): PRJNA313940PRJNA313939

REPOSITORIES: dbGaP

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Dataset's files

Source:

			Action	DRS
	GapExchange_phs001079.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001079.MalignantGlioblastoma.v1.p1.MULTI.pdf	Pdf
	manifest_phs001079.MalignantGlioblastoma.v1.p1.c1.GRU-IRB.pdf	Pdf
	datadict_v2.xsl	Other

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Project description:The differentiation and effector function of tumor infiltrating lymphocytes and macrophages in the tumor microenvironment is critical for productive anti-tumor immune responses, although direct evidence for this remains poorly characterized in brain cancer patients. Using mass cytometry, single-cell RNA sequencing, and quantitative multiplex immunofluorescence, we comprehensively characterized the phenotype and single-cell transcriptome of myeloid cells and T lymphocytes that infiltrated malignant gliomas, and identified how such populations changed following neoadjuvant PD-1 checkpoint blockade in recurrent glioblastoma patients. Cells of the myelo-monocytic lineage represented approximately three quarters of the immune cell infiltrate, with T lymphocytes representing the next major immune cell subset by density and percentage, but following neoadjuvant PD-1 antibody blockade, the ratio of myeloid cells to T cells significantly decreased. We then used single-cell RNA sequencing to comprehensively define the transcriptional profiles of lymphoid and myeloid populations in these tumors. Recurrent GBM patients treated with neoadjuvant PD-1 checkpoint inhibition possessed a greater fraction of CD8+ T cells with an effector T cell transcriptional program. The increased effector T cell populations were associated with the distinct upregulation of the chemokines, CXCL9 and CXCL10 by an interferon-responsive macrophage cluster. Importantly, we also identified that neoadjuvant PD-1 blockade was associated with significantly increased cellular interactions specifically between CD8+ T cells and tumor associated macrophages within the tumor microenvironment. Together, these findings suggest that effector T cell infiltration and differentiation are increased with neoadjuvant PD-1 blockade but impeded by adaptive resistance and immunosuppression from tumor associated macrophages. Future therapeutic strategies to target this dominant immunosuppressive myeloid cell population may be needed to achieve true, therapeutic interventions in this patient population.

Dataset Information

PD-1+ and PD-1- CD4+ Teff and Treg cells in Glioblastoma and Health

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