Gene Expression
Nebulas
Gene Expression NebulasSummary: Lung adenocarcinoma (LUAD)-derived oncogenic Wnts increase cancer cell proliferative/stemness potential, but whether they also impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. Wnt1 correlated strongly with tolerogenic genes on the TCGA expression data. In another cohort, Wnt1 was inversely associated with T cell abundance. Altering Wnt1 expression profoundly affected growth of murine lung adenocarcinomas and this was strongly dependent on conventional dendritic cells and T cells. Mechanistically, Wnt1 lead to transcriptional silencing of CC/CXC chemokines in dendritic cells and T cell cross-tolerance. Wnt-target genes were up-regulated in human intratumoral dendritic cells and decreased upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-loaded nanoparticles as single therapy or part of combinatorial immunotherapies acted at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 enhances adaptive immune rejection of lung adenocarcinomas and highlight its potential targeting as a novel therapeutic strategy
Overall Design: RNAseq data of two DC subsets of 4 patients with lung adenocarcinomas (LUADs).
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| Growth Protocol: | - |
| Treatment Protocol: | Primary LUADs and juxtatumor lung tissues were pushed through 40m strainers (Corning). CD45+ cells were magnetically enriched using CD45 Microbeads (Miltenyi Biotech), stained as described in Figure S16 and sorted in RL buffer (NorgenBioteck). |
| Extract Protocol: | RNA purification was performed with Norgen kit (NorgenBioteck) and cDNA synthesis with SMARter kit for Illumina Sequencing-HV(Clontech). |
| Library Construction Protocol: | Sequencing was performed in Illumina HiSeq 2500, the average depth is 15 million reads of 50-nt-length reads per sample. Library (paiRNAends fragments), sequencing and sequencing quality control were performed by the Institut Curie NGS plateform. |
| Molecule Type: | poly(A)+ RNA |
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| Library Layout: | PAIRED |
| Library Strand: | - |
| Platform: | ILLUMINA |
| Instrument Model: | Illumina HiSeq 2500 |
| Strand-Specific: | Unspecific |
| Data Resource | GEN Sample ID | GEN Dataset ID | Project ID | BioProject ID | Sample ID | Sample Name | BioSample ID | Sample Accession | Experiment Accession | Release Date | Submission Date | Update Date | Species | Race | Ethnicity | Age | Age Unit | Gender | Source Name | Tissue | Cell Type | Cell Subtype | Cell Line | Disease | Disease State | Development Stage | Mutation | Phenotype | Case Detail | Control Detail | Growth Protocol | Treatment Protocol | Extract Protocol | Library Construction Protocol | Molecule Type | Library Layout | Strand-Specific | Library Strand | Spike-In | Strategy | Platform | Instrument Model | Cell Number | Reads Number | Gbases | AvgSpotLen1 | AvgSpotLen2 | Uniq Mapping Rate | Multiple Mapping Rate | Coverage Rate |
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