Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE149826 | GEO | 2020/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (SMAC_RNAseq)

Project description:Immune checkpoint blockade (ICB) therapy has revolutionized the treatment of multiple cancers, but the majority of patients remain refractory due to impaired MHC-I expression. Although the combination of immunotherapy with existing anti-cancer treatments has shown synergy in multiple scenarios, the immunomodulatory effects of conventional therapies remain poorly understood. Here, we integrated CRISPR-mediated genetic screens and data mining of perturbation associated gene expression data to identify drugs that can specifically up-regulate MHC-I without inducing PD-L1. Using FACS-based genome-wide CRISPR screens, we identified Traf3, a critical suppressor of the NF-κB pathway, as a suppressor of MHC-I, but not PD-L1. A Traf3-knockout gene expression signature is associated with better survival in ICB-naive cancer patients and better response to ICB in published clinical trials. From publicly available drug treatment data, we identified SMAC mimetics as the top candidates of having similar transcriptional effects as Traf3-knockout. We experimentally validated that the SMAC mimetic birinapant specifically up-regulated MHC-I, sensitized cancer cells to T-cell-dependent killing, and synergized with ICB in the treatment of established tumors. Our findings provide a strong preclinical rationale for treating MHC-I-low tumors with SMAC mimetics to enhance sensitivity to existing immunotherapy. Moreover, the integrated approach used in this study can be generalized to identify drugs with immunomodulatory effects to enhance immunotherapy efficacy.

2020-07-01 | GSE149825 | GEO

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (koTRAF3_RNAseq)

2020-07-01 | GSE149824 | GEO

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (CRISPR_Screen)

2020-07-01 | GSE149822 | GEO

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (koTRAF3_ATACseq)

2020-07-01 | GSE149821 | GEO

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade

Project description:Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade

| PRJNA630229 | ENA

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (CRISPR_Screen)

Project description:Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (CRISPR_Screen)

| PRJNA630237 | ENA

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (SMAC_RNAseq)

Project description:Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (SMAC_RNAseq)

| PRJNA630239 | ENA

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (koTRAF3_ATACseq)

Project description:Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (koTRAF3_ATACseq)

| PRJNA630236 | ENA

Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (koTRAF3_RNAseq)

Project description:Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (koTRAF3_RNAseq)

| PRJNA630238 | ENA

Adipose PD-L1 Modulates PD-1/PD-L1 Checkpoint Blockade Immunotherapy Efficacy in Breast Cancer.

Project description:Programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) modulate antitumor immunity and are major targets of checkpoint blockade immunotherapy. However, clinical trials of anti-PD-L1 and anti-PD-1 antibodies in breast cancer demonstrate only modest efficacy. Furthermore, specific PD-L1 contributions in various tissue and cell compartments to antitumor immunity remain incompletely elucidated. Here we show that PD-L1 expression is markedly elevated in mature adipocytes versus preadipocytes. Adipocyte PD-L1 prevents anti-PD-L1 antibody from activating important antitumor functions of CD8+ T cells in vitro. Adipocyte PD-L1 ablation obliterates, whereas forced preadipocyte PD-L1 expression confers, these inhibitory effects. Pharmacologic inhibition of adipogenesis selectively reduces PD-L1 expression in mouse adipose tissue and enhances the antitumor efficacy of anti-PD-L1 or anti-PD-1 antibodies in syngeneic mammary tumor models. Our findings provide a previously unappreciated approach to bolster anticancer immunotherapy efficacy and suggest a mechanism for the role of adipose tissue in breast cancer progression.

| S-EPMC6209395 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data