Effects of the tumor microenvironment generated by glioblastoma multiforme cells over monocyte-derived dendritic cells

2019 ◽  
Vol 110 ◽  
pp. S31
Author(s):  
N. Chauca Torres ◽  
J. Marzagao Barbuto
Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4037
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil S. Sahajpal ◽  
Vamsi Kota ◽  
...  

Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer that accounts for almost 85% of lung cancer cases worldwide. Although recent advances in chemotherapy, radiotherapy, and immunotherapy have helped in the clinical management of these patients, the survival rate in advanced stages remains dismal. Furthermore, there is a critical lack of accurate prognostic and stratification markers for emerging immunotherapies. To harness immune response modalities for therapeutic benefits, a detailed understanding of the immune cells in the complex tumor microenvironment (TME) is required. Among the diverse immune cells, natural killer (NK cells) and dendritic cells (DCs) have generated tremendous interest in the scientific community. NK cells play a critical role in tumor immunosurveillance by directly killing malignant cells. DCs link innate and adaptive immune systems by cross-presenting the antigens to T cells. The presence of an immunosuppressive milieu in tumors can lead to inactivation and poor functioning of NK cells and DCs, which results in an adverse outcome for many cancer patients, including those with NSCLC. Recently, clinical intervention using modified NK cells and DCs have shown encouraging response in advanced NSCLC patients. Herein, we will discuss prognostic and predictive aspects of NK cells and DC cells with an emphasis on NSCLC. Additionally, the discussion will extend to potential strategies that seek to enhance the anti-tumor functionality of NK cells and DCs.


2013 ◽  
Vol 20 (8) ◽  
pp. 469-477 ◽  
Author(s):  
L Chen ◽  
J L Taylor ◽  
N C Sabins ◽  
D B Lowe ◽  
Y Qu ◽  
...  

Cancer Cell ◽  
2017 ◽  
Vol 31 (5) ◽  
pp. 614-615 ◽  
Author(s):  
Christina Pfirschke ◽  
Marie Siwicki ◽  
Hsin-Wei Liao ◽  
Mikael J. Pittet

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3028-3028 ◽  
Author(s):  
J. Nesselhut ◽  
D. R. Lorenzen ◽  
D. Marx ◽  
R. Y. Chang ◽  
C. Matthes ◽  
...  

3028 Background: The treatment of human cancer with monocyte-derived dendritic cells (MoDC) is a promising and innovative approach. However, many of the treated patients fail to respond to therapy. The reduced clinical antitumor response may be due to an inflammatory immune-suppressive tumor microenvironment. Regulatory T-cells (T-reg) and other cells with suppressive potential can promote an immune suppressive tumor microenvironment and thus play an important role in regulation of the immune response. Methods: Whole blood from n=100 cancer patients with various tumor types and from n=30 healthy donors were analysed by flow cytometry. CD4+ lymphocytes with immune suppressive potential were characterized by analysing the expression of CD25, CD39, CD127. Results: We found a significantly higher proportion of CD25+/CD39+ and of CD25+/CD127low T-helper cells in the blood of cancer patients as compared to healthy donors. This may indicate two different types of T-reg involved in immune suppression in cancer patients. Treatment of patients with metronomic chemotherapy induced a down-regulation of these cells. Interestingly, we found a subpopulation of cells within the lymphocyte gate characterized by CD2high and CD86 expression in cancer patients with very advanced stage, similar to such normally found in hemaphagocytic lymphohistiocytosis (HLH) patients characterized by exceeding high plasma concentration of IFN-g and IL-10 (Schneider et al. 2002). These cells can be down-regulated by treatment with a tetradecapeptide (Ezrin) known to act as an immune modulator with anti-viral activity leading to reduction of inflammatory cytokines. Conclusions: An efficient induction of a clinical antitumor response requires both a polarization of MoDC in a TH1 direction as well as changing an immune suppressive tumor microenvironment. For the first time, we identified HLH associated cells in advanced cancer patients. As HLH is characterized by hyperinflammation, these cells may indicate an inflammatory tumor microenvironment. Thus, anti-inflammatory therapy should be considered as co-treatment with immunotherapy with dendritic cells for down-regulation of immune suppressive cells (T-reg, CD2high/CD86+ cells) to promote a clinical antitumor response. No significant financial relationships to disclose.


2020 ◽  
Vol 218 (1) ◽  
Author(s):  
Genevieve M. Gerhard ◽  
Ruben Bill ◽  
Marius Messemaker ◽  
Allon M. Klein ◽  
Mikael J. Pittet

Dendritic cells (DCs) contribute a small fraction of the tumor microenvironment but are emerging as an essential antitumor component based on their ability to foster T cell immunity and immunotherapy responses. Here, we discuss our expanding view of DC heterogeneity in human tumors, as revealed with meta-analysis of single-cell transcriptome profiling studies. We further examine tumor-infiltrating DC states that are conserved across patients, cancer types, and species and consider the fundamental and clinical relevance of these findings. Finally, we provide an outlook on research opportunities to further explore mechanisms governing tumor-infiltrating DC behavior and functions.


2020 ◽  
Vol 217 (5) ◽  
Author(s):  
Yaoyao Shi ◽  
Wenxin Zheng ◽  
Kaiting Yang ◽  
Katharine G. Harris ◽  
Kaiyuan Ni ◽  
...  

Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 immunotherapy on tumor tissues through the capacity to accumulate within the tumor microenvironment. Systemic administration of Bifidobacterium leads to its accumulation within the tumor and converts the nonresponder mice into responders to anti-CD47 immunotherapy in a stimulator of interferon genes (STING)– and interferon-dependent fashion. Local delivery of Bifidobacterium potently stimulates STING signaling and increases cross-priming of dendritic cells after anti-CD47 treatment. Our study identifies the mechanism by which gut microbiota preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling.


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