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Changes in tumor infiltrating leukocytes following TA99 CAR T cell treatment

ABSTRACT: Changes in tumor infiltrating leukocytes following TA99 CAR T cell treatment

PROVIDER: PRJNA820291 | ENA |

REPOSITORIES: ENA

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Changes in tumor infiltrating leukocytes following TA99 CAR T cell treatment

Project description:Tumor infiltrating leukocytes were analyzed by scRNAseq 9 days after treatment with TA99 (anti-TRP-1) CAR T cells with or without Super2 and IL-33 co-expression.

2022-03-29 | GSE199491 | GEO

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Transcriptional signatures of tumor infiltrating CAR-T cells

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Project description:Murine tumour infiltrating lymphocytes (CD8+ T cells) were index-sorted based on expression of CD8a and CD3e. Subsequently cDNA was generated from these samples using the Smart-seq2 protocol. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

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Project description:Uveal melanoma (UM) with an inflammatory phenotype, characterized by infiltrating leukocytes and increased human leukocyte antigen (HLA) expression, carry an increased risk of death due to metastases. These tumors shoud be ideal for T-cell based therapies, yet it is not clear why prognostically-infaust tumors have a high HLA expression. We set out to determine whether the level of HLA molecules in UM is associated with other genetic factors, HLA transcriptional regulators, or microenvironmental factors. 28 enucleated UM were used to study HLA class I and II expression, and several regulators of HLA by immunohistochemistry, PCR microarray, qPCR and chromosome SNP-array. Fresh tumor samples of eight primary UM and four metastases were compared to their corresponding xenograft in SCID mice, using a PCR microarray and SNP array. Increased expression levels of HLA class I and II showed no dosage effect of chromosome 6p, but, as expected, were associated with monosomy of chromosome 3. Increased HLA class I and II protein levels were positively associated with their gene expression and with raised levels of the peptide-loading gene TAP1, and HLA transcriptional regulators IRF1, IRF8, CIITA, and NLRC5, revealing a higher transcriptional activity in prognostically-bad tumors. Implantation of fresh human tumor samples into SCID mice led to a loss of infiltrating leukocytes, and to a decreased expression of HLA class I and II genes , and their regulators. Our data provides evidence for a proper functioning HLA regulatory system in UM, offering a target for T-cell based therapies. NB: Here we show the PCR microarray (Illumina array).

2016-08-07 | GSE84976 | GEO

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