scholarly journals TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme—Future Perspectives

2020 ◽  
Vol 21 (9) ◽  
pp. 3114 ◽  
Author(s):  
Jakub Litak ◽  
Cezary Grochowski ◽  
Joanna Litak ◽  
Ida Osuchowska ◽  
Krzysztof Gosik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Immune Checkpoints ◽  
Toll Like Receptor ◽  
Future Perspectives ◽  
Programmed Death Ligand 1 ◽  
Incurable Disease ◽  
Programmed Death ◽  
Strong Relation ◽  
The Central Nervous System

Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.

scholarly journals LSD1/KDM1A, a Gate-Keeper of Cancer Stemness and a Promising Therapeutic Target

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1821 ◽  
Author(s):  
Panagiotis Karakaidos ◽  
John Verigos ◽  
Angeliki Magklara
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cellular Reprogramming ◽  
Future Perspectives ◽  
Cancer Stemness ◽  
Neuronal Stem Cells ◽  
Lysine Specific Demethylase ◽  
Promising Therapeutic Target ◽  
Exciting Area ◽  
Established Role

A new exciting area in cancer research is the study of cancer stem cells (CSCs) and the translational implications for putative epigenetic therapies targeted against them. Accumulating evidence of the effects of epigenetic modulating agents has revealed their dramatic consequences on cellular reprogramming and, particularly, reversing cancer stemness characteristics, such as self-renewal and chemoresistance. Lysine specific demethylase 1 (LSD1/KDM1A) plays a well-established role in the normal hematopoietic and neuronal stem cells. Overexpression of LSD1 has been documented in a variety of cancers, where the enzyme is, usually, associated with the more aggressive types of the disease. Interestingly, recent studies have implicated LSD1 in the regulation of the pool of CSCs in different leukemias and solid tumors. However, the precise mechanisms that LSD1 uses to mediate its effects on cancer stemness are largely unknown. Herein, we review the literature on LSD1’s role in normal and cancer stem cells, highlighting the analogies of its mode of action in the two biological settings. Given its potential as a pharmacological target, we, also, discuss current advances in the design of novel therapeutic regimes in cancer that incorporate LSD1 inhibitors, as well as their future perspectives.

scholarly journals Low CD8+ T Cell Infiltration and High PD-L1 Expression Are Associated with Level of CD44+/CD133+ Cancer Stem Cells and Predict an Unfavorable Prognosis in Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 541 ◽  
Author(s):  
Ya-Chin Hou ◽  
Ying-Jui Chao ◽  
Min-Hua Hsieh ◽  
Hui-Ling Tung ◽  
Hao-Chen Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
T Cells ◽  
Cancer Stem Cells ◽  
Cd8 T Cells ◽  
Death Receptor ◽  
Recurrence Risk ◽  
Immune Checkpoints ◽  
Prognostic Effect ◽  
A Minor

Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effects to evade immune system recognition. However, the clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC. Immunostaining and quantitative analysis were performed to assess CD8+ T cells infiltration, PD-L1 expression, and their relationship with CD44+/CD133+ CSCs and disease progression in PC. CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression group show high levels of CD44+/CD133+ CSCs, but patients with low CD8+ T cells infiltration/high PD-L1 expression had worse survival and higher recurrence risk than those with high CD8+ T cells infiltration/high PD-L1 expression. Moreover, high infiltration of CD8+ T cells could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/CD133. Our study highlights an interaction among CD8+ T cells infiltration, PD-L1 expression, and CD44+/CD133+ CSCs existence, which contributes to PC progression and immune evasion.

Cancer stem cells in radiation response: current views and future perspectives in radiation oncology

2019 ◽  
Vol 95 (7) ◽  
pp. 900-911 ◽  
Author(s):  
Claudia Peitzsch ◽  
Ina Kurth ◽  
Nadja Ebert ◽  
Anna Dubrovska ◽  
Michael Baumann
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Radiation Oncology ◽  
Radiation Response ◽  
Future Perspectives ◽  
Response Current

scholarly journals Low CD8+ T Cell Infiltration and High PD-L1 Expression Are Associated with CD44+/CD133+ Cancer Stem Cells and Predict an Unfavorable Prognosis in Pancreatic Cancer

2019 ◽  
Author(s):  
Ya-Chin Hou ◽  
Ying-Jui Chao ◽  
Min-Hua Hsieh ◽  
Hui-Ling Tung ◽  
Hao-Chen Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
T Cells ◽  
Cancer Stem Cells ◽  
Cd8 T Cells ◽  
Death Receptor ◽  
Recurrence Risk ◽  
Immune Checkpoints ◽  
Immune Recognition ◽  
Prognostic Effect

Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effect to evade the immune recognition. However, clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC. Immunostaining and quantitative analysis were performed to assess CD8+ T cells infiltration, PD-L1 expression, and their relationship with CD44+/CD133+ CSCs and disease progression in PC. CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression group show high levels of CD44+/CD133+ CSCs, but patients with low CD8+ T cells infiltration/high PD-L1 expression had worse survival and higher recurrence risk than those with high CD8+ T cells infiltration/high PD-L1 expression. Moreover, CD8+ T cells infiltration could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/CD133. Our study highlights an interaction among CD8+ T cells infiltration, PD-L1 expression, and CD44+/CD133+ CSCs existence, which contributes to PC progression and immune evasion.

Sign in / Sign up

Export Citation Format

Share Document