Dataset Information

Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model

ABSTRACT: A common cornerstone of preclinical cancer research is the use of syngeneic orthotopic murine tumors as immunocompetent models of human cancers. For glioblastoma research efforts, the GL261 and CT2A lines are frequently used. We systematically characterized these two lines to decipher the cell-intrinsic mechanisms that drive immuno-resistance in CT2A and to define the aspects of human cancer biology that the lines best model. We show that, despite sharing a few canonical genetic or histologic features of human glioblastoma, the transcriptional profiles of GL261 and CT2A tumours most closely resembled those of glioblastomas. CT2A additionally resembled other cancer types transcriptionally, including melanoma. CT2A displayed mesenchymal differentiation, upregulated angiogenesis, and multiple defects in antigen presentation machinery and interferon response pathways. Loss of MHC class I expression was restored in CT2A by interferon-γ treatment, explaining in part the modest efficacy of some immunotherapy combinations for CT2A. Our findings indicate that CT2A may serve as a robust preclinical solid tumor model of adaptive immune resistance.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Glioblastoma Cell

DISEASE(S): Glioblastoma

SUBMITTER: Ryuhjin Ahn

LAB HEAD: Forest White

PROVIDER: PXD036720 | Pride | 2023-12-19

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	CT2A_GL261_intracranial_GP_F.mzML	Mzml
	CT2A_GL261_intracranial_GP_F.mzid.gz	Mzid
	CT2A_GL261_intracranial_GP_F01.raw	Raw
	CT2A_GL261_intracranial_GP_F02.raw	Raw
	CT2A_GL261_intracranial_GP_F03.raw	Raw

Items per page:

1 - 5 of 40

Similar Datasets

Project description:MicroRNAs (miRNAs) are small (21-25 nucleotide in length) non-coding RNA molecules that negatively regulate protein expression. They are linked to cancer development and maintenance. In this work, studying gene expression profiles of 340 mammalian miRNAs with DNA microarrays, we selected 10 miRNAs gene features able to distinguish primary from secondary glioblastoma type; furthermore we verified that miR-21 and miR-155 up-regulatation seems to characterize the glioblastoma tumour state since it was found up-regulated in all samples analyzed compared to adult brain noneoplastic tissue. Since miR-21 function in glioblastoma cells was addressed previously we concentrated our efforts on miR-155 function. We found that miR-155 levels were markedly elevated both in primary and secondary glioblastomas tumours, in glioblastoma cell cultures and in 4 glioblastoma cell lines (U87, A172, LN229, and LN308) compared with adult brain tissue, CHP212-neuroblastoma cell lines and DAOY-1-medulloblastoma cell line. Since one of the miR-155 target was gamma-aminobutyric acid (GABA) A receptor (GABRA1) we verified if there was a relation between miR-155 up-regulation and GABRA1 expression. We demonstrated that, in cultured glioblastoma cells, knockdown of miR-155, which lower miR-155 expression to normal level, restore the normal expression of the gamma-aminobutyric acid (GABA) A receptor (GABRA1), making glioblastoma cells responsive to GABA cell cycle inhibiting signals. Our data suggest that aberrantly over-expressed miR-155 contribute to the malignant phenotype of the glioblastoma cells, promoting their unlimited growth. Keywords: miRNA expression profile We studied the expression profiles of 340 miRNAs in 97 glioblastoma tissues, of which 66 were primary glioblastomas and 27 were secondary glioblastomas. We have 66 replicates of primary glioblastoma and 27 replicates of secondary glioblastoma, each hybridized with the respective adult non-neoplastic brain tissue as a control.

Dataset Information

Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets