TNFSF13 Is a Novel Onco-Inflammatory Marker and Correlates With Immune Infiltration in Gliomas

Existing therapeutic strategies for gliomas are restricted; hence, exploration for novel diagnostic indicator and treatment is essential. Here, we performed bioinformatic analyses for TNFSF13 (also known as APRIL), a proliferation-inducing ligand of the tumor necrosis factor (TNF) superfamily, aiming to assess its potential for predicting glioma patient’s prognosis and targeted therapy. TNFSF13 expression was upregulated in the increase of tumor grades based on Xiangya cohort. In high TNFSF13 gliomas, somatic mutation was proved to correlate with amplification of EGFR and deletion of CDKN2A; while mutation of IDH1 was more frequently observed in low TNFSF13 group. We also confirmed the positive correlation between TNFSF13 and infiltrating immune and stromal cells in glioma microenvironment. Further, TNFSF13 was found to be involved in immunosuppression via diverse immunoregulation pathways and was associated with other immune checkpoints and inflammation. Single-cell sequencing revealed an abundant expression of TNFSF13 in neoplastic cells and M2 macrophages, which TNFSF13 might potentially regulate the cell communication via IL-8, C3, and CD44. Lastly, TNFSF13 mediated the activities of transcription factors including FOXO3, MEIS2, and IRF8. Our analyses demonstrated the relevance between TNFSF13 and glioma progress and indicated the potential of TNFSF13 as a novel diagnostic onco-inflammatory biomarker and immunotherapy target of gliomas.

Download Full-text

Orphan designation: autologous human adipose perivascular stromal cells genetically modified to secrete soluble tumour necrosis factor-related apoptosis-inducing ligand, The treatment of pancreatic cancer

Case Medical Research ◽

10.31525/cmr-bc1102 ◽

2019 ◽

Author(s):

Keyword(s):

Pancreatic Cancer ◽

Tumour Necrosis Factor ◽

Stromal Cells ◽

Tumour Necrosis ◽

Genetically Modified ◽

Orphan Designation ◽

Necrosis Factor

Download Full-text

From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽

10.3390/molecules26082278 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2278

Author(s):

Afshin Derakhshani ◽

Zeinab Rostami ◽

Hossein Safarpour ◽

Mahdi Abdoli Shadbad ◽

Niloufar Sadat Nourbakhsh ◽

...

Keyword(s):

Single Cell ◽

Signaling Pathways ◽

Immune Cells ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cancer Development ◽

Immune Checkpoints ◽

Single Cell Sequencing ◽

Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

Download Full-text

Aging of Bone Marrow Mesenchymal Stromal Cells: Hematopoiesis Disturbances and Potential Role in the Development of Hematologic Cancers

Cancers ◽

10.3390/cancers13010068 ◽

2020 ◽

Vol 13 (1) ◽

pp. 68

Author(s):

Fulvio Massaro ◽

Florent Corrillon ◽

Basile Stamatopoulos ◽

Nathalie Meuleman ◽

Laurence Lagneaux ◽

...

Keyword(s):

Bone Marrow ◽

Tumor Progression ◽

Cancer Progression ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Cell Communication ◽

Bone Marrow Niche ◽

Hematopoietic Stem ◽

Wide Range ◽

Major Player

Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression.

Download Full-text

1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer

Science Advances ◽

10.1126/sciadv.abe1174 ◽

2021 ◽

Vol 7 (4) ◽

pp. eabe1174

Author(s):

Marisa K. Kilgour ◽

Sarah MacPherson ◽

Lauren G. Zacharias ◽

Abigail E. Ellis ◽

Ryan D. Sheldon ◽

...

Keyword(s):

T Cells ◽

Immune Modulation ◽

Human Cancer ◽

Serous Carcinoma ◽

Necrosis Factor Alpha ◽

Methyl Group ◽

Cytokine Tumor Necrosis Factor ◽

Factor Alpha ◽

Immunotherapy Target ◽

Necrosis Factor

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer.

Download Full-text

Production of interleukin-6 in human osteoblasts and human bone marrow stromal cells: evidence that induction by interleukin-1 and tumor necrosis factor-alpha is not regulated by ovarian steroids.

Endocrinology ◽

10.1210/endo.136.9.7649114 ◽

1995 ◽

Vol 136 (9) ◽

pp. 4056-4067 ◽

Cited By ~ 57

Author(s):

L Rifas ◽

J S Kenney ◽

M Marcelli ◽

R Pacifici ◽

S L Cheng ◽

...

Keyword(s):

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Tumor Necrosis ◽

Interleukin 1 ◽

Marrow Stromal Cells ◽

Necrosis Factor Alpha ◽

Human Osteoblasts ◽

Ovarian Steroids ◽

Factor Alpha ◽

Necrosis Factor

Download Full-text

SHORT COMMUNICATION: Increased Expression of Glutathione by Estradiol, Tumor Necrosis Factor-Alpha, and Interleukin 1-Beta in Endometrial Stromal Cells

American Journal of Reproductive Immunology ◽

10.1111/j.1600-0897.2009.00760.x ◽

2009 ◽

Vol 62 (6) ◽

pp. 352-356 ◽

Cited By ~ 9

Author(s):

Sa Ra Lee ◽

Sung Hoon Kim ◽

Hoi Woul Lee ◽

Young-Hoon Kim ◽

Hee Dong Chae ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Stromal Cells ◽

Tumor Necrosis ◽

Short Communication ◽

Interleukin 1 ◽

Interleukin 1 Beta ◽

Endometrial Stromal Cells ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

Download Full-text

Comparative Study of Chemerin and Inflammatory markers between Obese with Insulin Resistance and lean healthy women

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00630 ◽

2021 ◽

pp. 3647-3650

Author(s):

Moushira Zaki ◽

Sanaa Kamal ◽

Mona Abd Elmotaleb A. Hussein ◽

Hend M. Tawfeek ◽

Mina Wassef Girgiss ◽

...

Keyword(s):

Insulin Resistance ◽

Inflammatory Marker ◽

Neutrophil To Lymphocyte Ratio ◽

Metabolic Parameters ◽

Low Grade ◽

Obese Women ◽

Fat Percentage ◽

Inflammatory Biomarker ◽

Lymphocyte Ratio ◽

Healthy Women

Background: Chemerin has been newly defined to be released from mature adipocytes and the chemerin concentrations in human serum augmented with obesity. There is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. The aim of this study is to expound the prospective role of chemerin the in inflammation. Also, investigate relation between chemerin and serum lipid, glucose, body fat percentage, and metabolic parameters in obese and lean women with IR. Lymphocytes and neutrophils play a major role in inflammation and comprise the first line of defense against infection. The ratio of absolute neutrophil count to lymphocyte count, the neutrophil-to-lymphocyte ratio (NLR), determined as is a novel inflammatory biomarker utilized as a prognostic factor in numerous diseases Methods: This study was designed to investigate serum chemerin, NLR, and high-sensitive C-reactive protein (hsCRP) levels in 50 obese women with IR and 50 lean healthy women. Results: Obese group had significant higher levels of serum chemerin, NLR, hsCRP levels and metabolic parameters than lean one. Chemerin also correlated positively with NLR inflammatory marker and body mass index (BMI). Neutrophil‐to‐lymphocyte ratio was related to pro‐inflammatory Conclusion: The present study elucidates that chemerin levels are concomitant with obesity and IR and could play a role in the inflammation, having key aspects of metabolic syndrome.

Download Full-text