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A burned-out CD8+ T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy

ABSTRACT: A burned-out CD8+ T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy

PROVIDER: PRJNA703970 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13764145_1.fastq.gz	Fastqsanger.gz
	SRR13764145_2.fastq.gz	Fastqsanger.gz
	SRR13764146_1.fastq.gz	Fastqsanger.gz
	SRR13764146_2.fastq.gz	Fastqsanger.gz
	SRR13764147_1.fastq.gz	Fastqsanger.gz

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A burned-out CD8+ T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy

Project description:Tumor-infiltrating lymphocytes (TILs) are considered to be exhausted, lacking proliferative and effector functions, which impairs cancer immunity. We employed single-cell mass cytometry and tissue imaging technologies to dissect TILs in 25 resectable and 35 advanced non-small cell lung cancer (NSCLC) patients. We identified a phenotypically burn-out CD8 TIL subset (Ebo), specifically accumulated within the tumor microenvironment (TME). In contrast to exhausted T-cells, Ebo appears to be the most proliferative TIL subset. Furthermore, Ebo showed the highest expression of activation markers, but it was more apoptotic and produced less IFNg than other CD8 TIL subsets. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-pathway dependent manner. Importantly, Ebo abundance in baseline tumor tissues was associated with resistance to anti-PD therapy in NSCLC patients. Our study identified a dysfunctional TIL subset, distinct from exhausted T-cells, and implies strategies to overcome resistance in cancer immunotherapy.

2021-02-23 | GSE167235 | GEO

A Burned-Out CD8<sup>+</sup> T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy.

Project description:Specific mechanisms by which tumor-infiltrating lymphocytes (TIL) become dysfunctional remain poorly understood. Here, we employed a two-pronged approach using single-cell mass cytometry and tissue imaging technologies to dissect TILs from 25 patients with resectable and 35 patients with advanced non-small cell lung cancer (NSCLC). We identified a burned-out CD8+ TIL subset (Ebo) that specifically accumulated within the tumor microenvironment (TME) but not in adjacent nontumoral tissues. Ebo showed the highest expression of proliferation and activation markers but produced the lowest amount of IFNγ and were the most apoptotic CD8+ TIL subset. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-1/B7-H1 pathway-dependent manner. Ebo abundance in baseline tumor tissues was associated with resistance to anti-PD therapy in patients with NSCLC. Our study identifies a dysfunctional TIL subset, with distinct features from previously described exhausted T cells, and implies strategies to overcome immunotherapy resistance. SIGNIFICANCE: We identified a highly proliferative, overactivated, and apoptotic dysfunctional CD8+ tumor-infiltrating subpopulation that is functionally distinct from previously described exhausted T cells. This population is expanded in lung cancer tissues in a PD-1/B7-H1-dependent manner, and its abundance is associated with resistance to cancer immunotherapy, thus becoming a potential tissue biomarker.This article is highlighted in the In This Issue feature, p. 1601.

| S-EPMC9421941 | biostudies-literature

Skeletal Muscle Transcriptome Is Affected By Age In Severely Burned Mice

Project description:Severe burn results in muscle wasting affecting quality of life in both children and adults. Biologic metabolic profiles are noticeably distinctive in childhood. We posit that muscle gene expression profiles are differentially regulated in response to severe burns in young animals. Twelve C57BL6 male mice, including young (5 weeks-old) and adults (11 weeks-old), received either scald burn, or sham procedure. Mouse muscle tissue was harvested 24 hours later for Next Generation Sequence (NGS) analysis. Our results showed 662 downregulated and 450 upregulated genes in gastrocnemius of young mice compared to adults without injury. After injury, we found 74/75 downregulated genes and 107/128 upregulated genes in both burned groups compared to respective uninjured age groups. VEGFA-VEGFR2, focal adhesion, and nuclear receptor meta-pathways were the top 3 gene pathways undergoing a differential change in response to age. Of note, the proteasome degradation pathway showed the most similar changes in both adult and young burned animals. This study demonstrates the characteristic profile of gene expression in skeletal muscle in young and adult burned mice. Prominent age effects were revealed in transcriptional levels with increased alterations of genes, miRNAs, pathways, and interactions.

2022-11-04 | GSE208548 | GEO

Metastatic "Burned Out" Seminoma Causing Neurological Paraneoplastic Syndrome-Not Quite "Burned Out".

Project description:A 44-year-old man presented with cerebellar ataxia and limbic encephalitis and was ultimately diagnosed with metastatic germ cell neoplasm resulting from a "burned out" primary testicular tumor. The patient had progressive ataxia, leading to a thorough investigation for infectious, autoimmune, metabolic, and malignant causes of acquired cerebellar ataxia that revealed no significant findings. Testicular sonography demonstrated a possible right testicular lesion that was not confirmed on radical inguinal orchiectomy. F18-FDG positron emission tomography/computerized tomography scan revealed a solitary retroperitoneal lesion, concerning for metastatic disease but not amenable to percutaneous biopsy. A robotic retroperitoneal lymph node dissection was performed and pathology revealed a CD117-positive metastatic seminoma leading to appropriate germ cell tumor-directed chemotherapy. After completing chemotherapy and during 1 year of follow-up, there has been a gradual improvement of the patient's neurological manifestations.

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Metatranscripts from laboratory-burned soil

Project description:Metatranscripts from laboratory-burned soil: raw sequence reads

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TXNIP loss expands Myc transcriptome

Project description:TXNIP loss expands Myc transcriptome

| PRJNA923027 | ENA

Adipocyte serine uptake curbs ROS generation and visceral adiposity

Project description:Adipocyte serine uptake curbs ROS generation and visceral adiposity

| PRJNA557596 | ENA

3’ Uridylation Expands miRNA Target Repertoire

Project description:3’ Uridylation Expands miRNA Target Repertoire

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Differentially expressed miRNA in burned murine skin tissue compared to normal skin tissue

Project description:Interactions between stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXCR4 are crucial for the recruitment of mesenchymal stem cells (MSCs) from bone marrow (BM) reservoirs to damaged tissues for repair during alarm situations. MicroRNAs are differentially expressed in stem cell niches, suggesting a specialized role in stem cell regulation. Here, we gain insight into the molecular mechanisms involved in regulating SDF-1α. Individualized outcome prediction classifiers were successfully constructed through expression profiling of microRNAs (in all organisms as annotated in Sanger miRBase Release 11.0 (http://microrna.sanger.ac.uk))in one burned murine skin tissue compared to normal skin tissue,which had 57 upregulated microRNAs and 28 down-regulated microRNAs.

2013-05-02 | GSE46558 | GEO

Adipocyte serine uptake curbs ROS generation and visceral adiposity [Human]

Project description:Adipocyte serine uptake curbs ROS generation and visceral adiposity [Human]

| PRJNA557598 | ENA