Simultaneous T Cell Activation and Macrophage Polarization to Promote Potent Tumor Suppression by Iron Oxide‐Embedded Large‐Pore Mesoporous Organosilica Core–Shell Nanospheres

2019 ◽  
Vol 8 (9) ◽  
pp. 1900039 ◽  
Author(s):  
Lin Chen ◽  
Xiaobo Ma ◽  
Meng Dang ◽  
Heng Dong ◽  
Hongming Hu ◽  
...  
Keyword(s):  
Iron Oxide ◽  
T Cell ◽  
T Cell Activation ◽  
Tumor Suppression ◽  
Cell Activation ◽  
Macrophage Polarization ◽  
Core Shell ◽  
Large Pore ◽  
Mesoporous Organosilica ◽  
Potent Tumor

847 Inflammasome activation in M2 macrophage restrain the immune suppressive function

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A900-A900
Author(s):  
Ronghua Zhang ◽  
Tienan Wang ◽  
Qing Lin
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Culture System ◽  
Cell Activation ◽  
Macrophage Polarization ◽  
Inflammasome Activation ◽  
M2 Macrophage ◽  
M1 Macrophage ◽  
Suppressive Phenotype

BackgroundMacrophage is an important component in tumor microenvironment (TME) and plays multiple roles in tumor initiation, progression and metastases. In response to various stimuli within TME, macrophage exhibits high level of functional heterogeneity. There are two distinct groups of macrophages: M1 macrophage exhibits pro-inflammatory phenotype with high levels of TNF-a, IL-6, and IL-1ß, while M2 macrophage displays immune suppressive phenotype with high levels of anti-inflammatory cytokines such as IL-10 and TGF-ß. In response to the M2 cytokines, myeloid cells within the TME further acquire higher expression of PD-L1 and thus inactivate T cells. M2 cytokines can also directly inhibit T cell activation. As a result, re-polarizing M2 macrophages becomes a key concept for cancer immunotherapy. The NLRP3 inflammasome is acquired by macrophages to fight against endogenous danger signals. Macrophage NLRP3 activation has been observed in several tumor models, but the function of NLRP3 on macrophage polarity remains controversial. Inflammasome activation with IL-1ß/IL-18 secretion was reported to promote M1 polarization. However, NLRP3 activation was also reported to promote M2 polarity through up-regulation of IL4 in asthma modelMethodsHere, we have established an in vitro human macrophage NLRP3 activation system (figure 1), coupled with M2 macrophage polarization assay, to dissect the role of NLRP3 in macrophage phenotype.ResultsOur results indicate that NLRP3 activation restrained M2 phenotype and further enhanced T cell activation in an M2/T cell co-culture system (figure 2).Abstract 847 Figure 1Inflammasome activation polarize M2 macrophage intUse LPS/ATP to stimulate NLRP3 in M2 macrophage and demonstrate NLRP3 activation could reduce CD163 and increase CD86Abstract 847 Figure 2Inflammasome in M2 rescue T cell activationestablish M2/T co-culture system in vitro to demonstrate M2 could suppress T activation while Inflammatory M2 could partial rescue the suppressive phenotypeConclusionsInflammasome could be the potential target for cancer by modulating T cell activation through macrophage polarization regulation

scholarly journals Reactive Oxygen Species in Anticancer Immunity: A Double-Edged Sword

2021 ◽  
Vol 9 ◽  
Author(s):  
Jie Wang ◽  
Ning Liu ◽  
Hongfei Jiang ◽  
Qian Li ◽  
Dongming Xing
Keyword(s):  
Reactive Oxygen Species ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Clinical Success ◽  
Macrophage Polarization ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Physiological Processes ◽  
Anticancer Immunity

Reactive oxygen species (ROS) are critical mediators in many physiological processes including innate and adaptive immunity, making the modulation of ROS level a powerful strategy to augment anticancer immunity. However, current evidences suggest the necessity of a deeper understanding of their multiple roles, which may vary with their concentration, location and the immune microenvironment they are in. Here, we have reviewed the reported effects of ROS on macrophage polarization, immune checkpoint blocking (ICB) therapy, T cell activation and expansion, as well as the induction of immunogenic cell death. A majority of reports are indicating detrimental effects of ROS, but it is unadvisable to simply scavenge them because of their pleiotropic effects in most occasions (except in T cell activation and expansion where ROS are generally undesirable). Therefore, clinical success will need a clearer illustration of their multi-faced functions, as well as more advanced technologies to tune ROS level with high spatiotemporal control and species-specificity. With such progresses, the efficacy of current immunotherapies will be greatly improved by combining with ROS-targeted therapies.

scholarly journals MiR‐16 regulates mouse peritoneal macrophage polarization and affects T‐cell activation

2016 ◽  
Vol 20 (10) ◽  
pp. 1898-1907 ◽  
Author(s):  
Xiaoqin Jia ◽  
Xiaomin Li ◽  
Yating Shen ◽  
Junjun Miao ◽  
Hao Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Peritoneal Macrophage ◽  
T Cell Activation ◽  
Cell Activation ◽  
Macrophage Polarization ◽  
Mouse Peritoneal Macrophage

scholarly journals Osteopontin: A Key Regulator of Tumor Progression and Immunomodulation

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3379
Author(s):  
Hannah R. Moorman ◽  
Dakota Poschel ◽  
John D. Klement ◽  
Chunwan Lu ◽  
Priscilla S. Redd ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Patients ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Cancer ◽  
Macrophage Polarization ◽  
Elevated Serum ◽  
Lymphoid Cells ◽  
Wide Range

OPN is a multifunctional phosphoglycoprotein expressed in a wide range of cells, including osteoclasts, osteoblasts, neurons, epithelial cells, T, B, NK, NK T, myeloid, and innate lymphoid cells. OPN plays an important role in diverse biological processes and is implicated in multiple diseases such as cardiovascular, diabetes, kidney, proinflammatory, fibrosis, nephrolithiasis, wound healing, and cancer. In cancer patients, overexpressed OPN is often detected in the tumor microenvironment and elevated serum OPN level is correlated with poor prognosis. Initially identified in activated T cells and termed as early T cell activation gene, OPN links innate cells to adaptive cells in immune response to infection and cancer. Recent single cell RNA sequencing revealed that OPN is primarily expressed in tumor cells and tumor-infiltrating myeloid cells in human cancer patients. Emerging experimental data reveal a key role of OPN is tumor immune evasion through regulating macrophage polarization, recruitment, and inhibition of T cell activation in the tumor microenvironment. Therefore, in addition to its well-established direct tumor cell promotion function, OPN also acts as an immune checkpoint to negatively regulate T cell activation. The OPN protein level is highly elevated in peripheral blood of human cancer patients. OPN blockade immunotherapy with OPN neutralization monoclonal antibodies (mAbs) thus represents an attractive approach in human cancer immunotherapy.

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