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Expression data of B lymphocytes isolated from C57BL/6 Tilcara (Til) mouse mutant compared with wild-type C57BL/6 mouse [microarray]

ABSTRACT: Recent studies show that PKCs can have a nuclear function as epigenetic enzymes to directly regulate gene expression in the immune system. Using a PKCβ mutant mice model, C57BL/6 Tilcara (Til) mouse mutant, we examined the role of PKCβ as a histone kinase in regulating inducible gene expression in immune cells. We investigated if PKCβ is important for the expression of key inducible genes upon B cell activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE137465 | GEO | 2022/09/14

REPOSITORIES: GEO

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Genome-wide mapping of histone H3 T6 phosphorylation in mouse B lymphocytes [ChIP-seq]

Project description:The changes in gene expression can be epigenetically regulated by histone modifications. As PKCB is known to phosphorylate H3T6 leading to gene activation, we examined if the changes in gene expression seen in B cell activation were associated with H3T6 phosphorylation. We want to examine how PKCB mutation will affect H3T6 phosphorylation on a genome-wide level and so we performed ChIP-seq with H3T6 phosphorylation in wildtype and C57BL/6 Tilcara (Til) mouse, a PKCβ mutant mice model.

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Expression data of B lymphocytes isolated from C57BL/6 Tilcara (Til) mouse mutant compared with wild-type C57BL/6 mouse [microarray]

Project description:Expression data of B lymphocytes isolated from C57BL/6 Tilcara (Til) mouse mutant compared with wild-type C57BL/6 mouse [microarray]

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Autologous Tumor Infiltrating Lymphocytes MDA-TIL in Treating Patients With Recurrent or Refractory Ovarian Cancer, Colorectal Cancer, or Pancreatic Ductal Adenocarcinoma

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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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Project description:Purpose: Human papilloma virus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than HPV(-) negative cancer. This may be due, in part, to the higher number of tumour infiltrating lymphocytes (TIL) in HPV(+) tumours. We used RNAseq to evaluate whether these differences in clinical behaviour could be explained simply by a numerical difference in TILs or whether there was a fundamental difference between TILs in these two settings. Patients and methods: Twenty-three consecutive HNSCC cases with high and moderate TIL density were subjected to RNAseq analysis. Differentially expressed genes (DEG) between 10 HPV(+) and 13 HPV(-) tumours were identified with EdgeR. Immune subset analysis was performed using, FAIME (Functional Analysis of Individual Microarray Expression) and Immune gene transcript count analysis. Results: 1634 genes were differentially expressed. There was a dominant immune signature in HPV(+) tumours. After normalizing expression profiles for numerical differences in T cells and B cells, 437 significantly DEGs still remained. A B-cell associated signature emerged, which segregated HPV(+) from HPV(-) cancers and included CD200, STAG3, GGA2, SPIB and ADAM28. Differential expression of these genes was confirmed by real-time quantitative PCR and immunohistochemistry. Conclusion: In our dataset, the difference associated with T-cells between patients with HPV(+) and (-) HNSCC was predominantly numerical. However, when TIL numbers are corrected, a distinct differential B-cell signature was revealed. mRNA profiles of 10 HPV driven (HPV+) and 13 HPV independant (HPV-) head and neck squamous cell carcinoma (HNSCC) tumours were generated by RNA-Seq, using Illumina HiSeq 2000.

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