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A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers

ABSTRACT: A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers

PROVIDER: PRJNA475178 | ENA |

REPOSITORIES: ENA

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A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers

Project description:A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers

| PRJNA475179 | ENA

A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers.

Project description:The biological determinants of sensitivity and resistance to immune checkpoint blockers are not completely understood. To elucidate the role of intratumoral T-cells and their association with the tumor genomic landscape, we perform paired whole exome DNA sequencing and multiplexed quantitative immunofluorescence (QIF) in pre-treatment samples from non-small cell lung carcinoma (NSCLC) patients treated with PD-1 axis blockers. QIF is used to simultaneously measure the level of CD3+ tumor infiltrating lymphocytes (TILs), in situ T-cell proliferation (Ki-67 in CD3) and effector capacity (Granzyme-B in CD3). Elevated mutational load, candidate class-I neoantigens or intratumoral CD3 signal are significantly associated with favorable response to therapy. Additionally, a "dormant" TIL signature is associated with survival benefit in patients treated with immune checkpoint blockers characterized by elevated TILs with low activation and proliferation. We further demonstrate that dormant TILs can be reinvigorated upon PD-1 blockade in a patient-derived xenograft model.

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Transcriptional changes in dormant and non_dormant potato meristems

Project description:RNA was sequenced from meristems excised from dormant and non-dormant potato tubers harvested from four different harvest years. Expression based on mapped RNA-sequences was accomplished from excised meristems from fall harvested (dormant tubers) and the same harvested tubers were stored under standard commercial conditions until sprouting was present (non-dormant). The experiment was replicated for four different harvest years.

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Response of unmodified and TGFBR2 knockout tumor infiltrating lymphocytes (TIL) to TGF-B stimulation

Project description:TGFBR2 was deleted in ovarian cancer TIL via CRISPR/Cas9 gene editing. Response of unmodified and TGFBR2 knockout TIL to TGF-B stimulation was evaluated via RNA sequencing.

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Transcriptomic analysis of CV. ‘Shine Muscat’ (Vitis vinifera L.) buds during dormant and non dormant period

Project description:We used Illumina RNA-Seq technology to carry out digital gene expression profiling of Dormant and non dormant buds of Shine Muscat Cultivar.127 pathways were annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and metabolic, biosynthesis of secondry metabolite and. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were involved in various metabolic processes, including phytohormone metabolism. The newly generated transcriptome and gene expression profiling data provide valuable genetic information for revealing transcriptomic variation during dormant and non dormant period in Grapevine and ultimately helpful in uplifting of table grape industry.

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Identifying dormant cells in colorectal cancer spheroids

Project description:Cellular dormancy and heterogeneous cell cycle lengths provide important explanations for treatment failure following adjuvant therapy with S-phase cytotoxics in colorectal cancer (CRC) yet the molecular control of the dormant versus cycling state remains unknown. In CRCs dormant cells are found to be highly clonogenic and resistant to chemotherapies. We sought to understand the molecular features of dormant CRC cells to facilitate rationale identification of compounds to target both dormant and cycling tumour cells.

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Stimulation of tumor infiltrating B-cells improves ex-vivo TIL expansion for melanoma sample immunotherapy I

Project description:Many studies have shown association of tumor infiltrating B-cells and presence of tertiary lymphoid structure with improved clinical responses to immune checkpoint inhibitors therapy. We hypothesized that their presence could also have an impact on TIL therapy response. To address this, we performed RNA-seq of FFPE samples from a cohort of patients that received TIL therapy. Melanoma tumors collected prior to TIL infusion were evaluated for immune content in 9 responders and 11 non-responders to TIL therapy. Our data demonstrate an increase in class-switched memory B-cells in responders compared with non-responders to TIL therapy. In the myeloid compartment, increased presence of dendritic cell populations (pDC, aDC, and iDC) and basophils was observed in responders to TIL therapy, as well as higher content of γδ T cells and effector memory CD8+ T cells (CD8+ Tem) in the T-cell compartment. Next, we assessed the TLS presence in the same cohort by a gene expression signature of 12 chemokines using principal component analysis. The responders showed a higher TLS score compared with the non-responder patients, suggesting that patients responding to TIL therapy had more TLS in their tumors than the non-responder patients. These observations indicate that, same as in the immune checkpoint inhibitors therapy response, presence of B-cells and TLS might have a positive impact in the clinical outcome to TIL therapy.

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