Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells

ABSTRACT: We evaluated whether there are transcriptional differences between RNF31-proficient immune-resistant and RNF31-deficient immune-sensitive tumor cells. We stimulated sensitive (sgRNF31- or HOIPIN-8-treated) and resistant (sgCtl, vehicle) BLM tumor cells with TNF for 0 or 6 hours and performed RNA sequencing analysis. Tumor cells sensitized by RNF31 inhibition show a reduced canonical NF-kB and increased pro-death signature upon TNF challenge.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186396 | GEO | 2022/05/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells

Project description:Tumor escape mechanisms for immunotherapy include deficiencies in antigen presentation, diminishing adaptive CD8+ T cell antitumor activity. Although innate NK cells are triggered by loss of MHC class I, their response is often inadequate. To increase tumor susceptibility to both innate and adaptive immune elimination, we performed parallel genome-wide CRISPR-Cas9 screens. This identified all components, RNF31, RBCK1, and SHARPIN, of the linear ubiquitination chain assembly complex (LUBAC). Genetic and pharmacologic ablation of RNF31, an E3 ubiquitin ligase, strongly sensitized melanoma, breast and colorectal cancer cells to both NK and CD8+ T cell killing. This occurred in a TNF-dependent manner, causing loss of A20 and non-canonical IKK complexes from TNF Receptor Complex I. Corroborating this preclinically, a small molecule RNF31 inhibitor sensitized human colon carcinoma organoids to TNF and greatly enhanced immune bystander killing of antigen-loss and antigen presentation machinery-deficient tumor cells. These results merit exploration of RNF31 inhibition as a clinical pharmacological opportunity for immunotherapy-refractory cancers.

2022-05-30 | PXD029489 | Pride

RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells

Project description:RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells

| PRJNA773728 | ENA

RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells.

Project description: Not available

| S-EPMC9245005 | biostudies-literature

Genome-wide CRISPR screen to identfy immune evasion genes in pancreatic cancer

Project description:Here we systematically dissected PDA intrinsic mechanisms of immune evasion by in vitro and in vivo CRISPR screening. Beyond the conserved set of genes regulating anti-cancer immunity we identified Rnf31 and Vps4b as essential factors required for escaping CD8+ T cell-killing. While the absence of Rnf31 induced sensitivity to T cell killing through TNF-mediated apoptosis in murine cancer cells and human PDA organoids, loss of Vps4b abrogated functional autophagy, resulting in accumulation of CD8+ T cell-derived granzyme B and subsequent tumor cell lysis.

2021-07-27 | GSE180834 | GEO

Targeting Glycomes Sensitizes Ovarian Tumors to Immune Checkpoint Blockade

Project description:Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, homologous recombination (HR) status-dependent glycosylation has never been explored therapeutically. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe a unique enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their resistance to anti-PD-L1 by enhancing its binding with PD-1 on CD8_ T cells. In orthotopic syngeneic EOC mouse models, inhibiting branched N-glycans, using 2-Deoxy-D-glucose, sensitizes HR-proficient, but not HR-deficient EOCs, to anti-PD-L1. These findings indicate branched N-glycans as promising therapeutic targets whose inhibition sensitizes HR-proficient EOCs to ICB by overcoming immune evasion

2024-03-11 | GSE244012 | GEO

Exploration of the mechanisms underlying TNF-alpha resistance in breast cancer cells by a transcriptomic approach using an autophagy-dedicated microarray.

Project description:We used the autophagy microarray to profile the transcriptome of well-characterized TNF sensitive MCF-7 cell line and corresponding TNF-resistant 1001 clone.

2011-02-28 | E-MEXP-3074 | biostudies-arrayexpress

Sensitizing Resistant Cancer Cells to T cell-secreted Cytokines

Project description:Tumor heterogeneity is a major barrier to cancer therapy, including immunotherapy. Activated T cells can efficiently kill tumor cells following recognition of MHC class I (MHC-I) bound peptides, but this selection pressure favors outgrowth of MHC-I deficient tumor cells. We performed a genome-scale screen to discover alternative pathways for T cell-mediated killing of MHC-I deficient tumor cells. Autophagy and TNF signaling emerged as top pathways, and inactivation of Rnf31 (TNF signaling) and Atg5 (autophagy) sensitized MHC-I deficient tumor cells to apoptosis by T cell-derived cytokines. Mechanistic studies demonstrated that inhibition of autophagy amplified pro-apoptotic effects of cytokines in tumor cells. Antigens from apoptotic MHC-I deficient tumor cells were efficiently cross-presented by dendritic cells, resulting in heightened tumor infiltration by IFNg and TNFa-producing T cells. Tumors with a substantial population of MHC-I deficient cancer cells could be controlled by T cells when both pathways were targeted using genetic or pharmacological approaches.

2022-09-13 | GSE213078 | GEO

Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition

Project description:Leukemia cells resistant to standard treatment are sensitive to a recently developed inhibitor of mitochondrial gene expression.

2022-09-26 | GSE213976 | GEO

Transcription profiling of human TRAIL-resistant metastatic vs primary TRAIL-sensitive melanoma cells

Project description:T1 and G1 are the two melanoma cell lines, established from primary tumor (T1) and lymph node metastases (G1) of a 77 years old male patient. While G1 cells were resistant to TRAIL (TNF-related apoptosis-inducing ligand) mediated cell death, T1 cells exhibited a high dose- and time-dependent sensitivity to TRAIL. Cells were treated with or without of two doses (0.2 and 1ug/ml) of TRAIL for 24 h. Gene expression of each sample vs pool was measured. TRAIL-resistant metastatic G1 vs primary TRAIL-sensitive T1 was compared.

2006-01-01 | E-MEXP-247 | biostudies-arrayexpress

Gap junctions mediate human immunodeficiency virus-bystander killing in astrocytes.

Project description: Not available

| S-EPMC2117380 | biostudies-literature