scholarly journals Identification of immunologic subtype and prognosis of GBM based on TNFSF14 and immune checkpoint gene expression profiling

Aging ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 7112-7128
Author(s):  
Shengrong Long ◽  
Mingdong Li ◽  
Jia Liu ◽  
Yi Yang ◽  
Guangyu Li
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Immune Checkpoint ◽  
Expression Profiling ◽  
Checkpoint Gene

scholarly journals 603 Targeted STAT3 degradation leads to remodeling of an immunosuppressive tumor microenvironment and subsequent sensitization to immune checkpoint therapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A633-A633
Author(s):  
Joyoti Dey ◽  
Phillip Liu ◽  
Michele Mayo ◽  
Rahul Karnik ◽  
Bin Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Gene Expression Profiling ◽  
Cancer Cell ◽  
Immune Checkpoint ◽  
Expression Profiling ◽  
Immune Cell ◽  
B Cell Lymphoma ◽  
Activation Markers

BackgroundSignal Transducer and Activator of Transcription 3 (STAT3), a multifaceted transcription factor, is aberrantly activated across a variety of malignancies; however, its selective targeting has to-date remained a therapeutic challenge. STAT3 plays a pivotal role in shaping the tumor immune landscape through cancer cell-intrinsic mechanisms, direct regulation of immune cell function and via cancer cell- tumor microenvironment (TME) crosstalk, that collectively result in an immunosuppressive TME. Targeted protein degradation represents a novel therapeutic modality enabling direct targeting of previously undruggable oncoproteins. We have developed potent and selective STAT3 heterobifunctional degraders demonstrating activity across diverse tumor and immune cell types.MethodsWe investigated the immunomodulatory impact of STAT3 degradation on tumorigenesis in syngeneic mouse models representing cancers with heterogeneous immune milieus. Methods included in vivo pharmacological approaches, immunophenotyping and gene expression profiling.ResultsTreatment of CT-26 (colorectal cancer) and A20 (B-cell lymphoma) tumor-bearing mice with a STAT3 degrader resulted in significant tumor growth inhibition compared to controls, with loss of STAT3 protein in both tumor cells and TME. This was accompanied by a decrease in M2 polarized macrophages and concomitant increases in M1 polarized macrophages and tumor infiltrating lymphocytes. The anti-tumor responses were abrogated by antibody mediated CD8+ T cell depletion or by using immunodeficient host-strains implicating the observed efficacy to be predominantly driven by immune-directed mechanisms. Gene expression profiling of STAT3 degrader-treated CT-26 tumors showed marked increases in proinflammatory genes including T cell and M1 macrophage activation markers, compared to controls. Notably, induction of an Ifnγ-responsive gene signature (Ifnγ, Stat1, Cxcl9, Cxcl10, Ido1) suggested that STAT3 degradation results in a T-cell inflamed phenotype associated with responsiveness to immune checkpoint therapy (ICT). Furthermore, on-treatment tumors showed an upregulation of genes such as Pdl1, Ctla4, Lag3 which reflect T cell activation as well as counterregulatory mechanisms. Therefore, we evaluated STAT3 degradation in combination with anti-PD1 in these models which are poorly responsive to anti-PD1 monotherapy. Robust synergy was observed in the CT-26 model with 60% complete responses and development of immunological memory as confirmed by tumor re-challenge studies. Studies are underway to ascertain the applicability of this combination therapy in different tumor-immune contextures and indications, and to elucidate the mechanistic basis of synergy.ConclusionsSTAT3 degradation remodels an immunosuppressed TME activating anti-tumor immunity as monotherapy and effectively combines with anti-PD1. These data provide a rationale for selectively degrading STAT3 as a strategy to sensitize cancers with relevant immune contextures to ICT in the clinic.

Custom microarray for glycobiologists: considerations for glycosyltransferase gene expression profiling

2002 ◽  
Vol 69 ◽  
pp. 135-142 ◽  
Author(s):  
Elena M. Comelli ◽  
Margarida Amado ◽  
Steven R. Head ◽  
James C. Paulson
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Affymetrix Genechip ◽  
Microarray Technology ◽  
Gene Arrays ◽  
Glycosyltransferase Gene

The development of microarray technology offers the unprecedented possibility of studying the expression of thousands of genes in one experiment. Its exploitation in the glycobiology field will eventually allow the parallel investigation of the expression of many glycosyltransferases, which will ultimately lead to an understanding of the regulation of glycoconjugate synthesis. While numerous gene arrays are available on the market, e.g. the Affymetrix GeneChip® arrays, glycosyltransferases are not adequately represented, which makes comprehensive surveys of their gene expression difficult. This chapter describes the main issues related to the establishment of a custom glycogenes array.

278: Gene Expression Profiling of Prostatic Epithelial Cells in Two-Dimensional Versus Three-Dimensional Cultures

2007 ◽  
Vol 177 (4S) ◽  
pp. 93-93
Author(s):  
Toshiyuki Tsunoda ◽  
Junichi Inocuchi ◽  
Darren Tyson ◽  
Seiji Naito ◽  
David K. Ornstein
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Three Dimensional ◽  
Two Dimensional

748: Gene Expression Profiling of Renal Medullary Carcinoma

2004 ◽  
Vol 171 (4S) ◽  
pp. 198-199 ◽  
Author(s):  
Ximing J. Yang ◽  
Jun Sugimura ◽  
Maria S. Tretiakova ◽  
Bin T. Teh
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Medullary Carcinoma ◽  
Renal Medullary Carcinoma
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