scholarly journals Cancer Immunotherapy: Simultaneous T Cell Activation and Macrophage Polarization to Promote Potent Tumor Suppression by Iron Oxide‐Embedded Large‐Pore Mesoporous Organosilica Core–Shell Nanospheres (Adv. Healthcare Mater. 9/2019)

2019 ◽  
Vol 8 (9) ◽  
pp. 1970041
Author(s):  
Lin Chen ◽  
Xiaobo Ma ◽  
Meng Dang ◽  
Heng Dong ◽  
Hongming Hu ◽  
...  
Keyword(s):  
Iron Oxide ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
T Cell Activation ◽  
Tumor Suppression ◽  
Cell Activation ◽  
Macrophage Polarization ◽  
Core Shell ◽  
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 A Dual Immunotherapy Nanoparticle Improves T‐Cell Activation and Cancer Immunotherapy

2018 ◽  
Vol 30 (25) ◽  
pp. 1706098 ◽  
Author(s):  
Yu Mi ◽  
Christof C. Smith ◽  
Feifei Yang ◽  
Yanfei Qi ◽  
Kyle C. Roche ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
T Cell Activation ◽  
Cell Activation

scholarly journals Microfluidic On-demand Engineering of Exosomes towards Cancer Immunotherapy

2018 ◽  
Author(s):  
Zheng Zhao ◽  
Jodi McGill ◽  
Mei He
Keyword(s):  
Cell Culture ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Real Time ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tumor Antigens ◽  
Parent Cell ◽  
Melanoma Tumor ◽  
Microfluidic Cell Culture

Extracellular Vesicles (EVs), particularly exosomes (30-150 nm), are an emerging delivery system in mediating cellular communications, which have been observed for priming immune responses by presenting parent cell signaling proteins or tumor antigens to immune cells. Therefore, preparation of antigenic exosomes that can play therapeutic roles, particularly in cancer immunotherapy, is emerging. However, standard benchtop methods (e.g., ultracentrifugation and filtration) lack the ability to purify antigenic exosomes specifically among other microvesicle subtypes, due to the non-selective and time-consuming (>10 h) isolation protocols. Exosome engineering approaches, such as the transfection of parent cells, also suffer from poor yield, low purity, and time-consuming operations. In this paper, we introduce a streamlined microfluidic cell culture platform for integration of harvesting, antigenic modification, and photo-release of surface engineered exosomes in one workflow, which enables the production of intact, MHC peptide surface engineered exosomes for cytolysis activation. The PDMS microfluidic cell culture chip is simply cast from a 3D-printed mold. The proof-of-concept study demonstrated the enhanced ability of harvested exosomes in antigen presentation and T cell activation, by decorating melanoma tumor peptides on the exosome surface (e.g., gp-100, MART-1, MAGE-A3). Such surface engineered antigenic exosomes were harvested in real-time from the on-chip culture of leukocytes isolated from human blood, leading to much faster cellular uptake. The activation of gp100-specific CD8 T cells which were purified from the spleen of 2 Pmel1 transgenic mice was evaluated using surface engineered exosomes prepared from muring antigen presenting cells. Antigen-specific CD8 T cell proliferation was significantly induced by the engineered exosomes compared to native, non-engineered exosomes. This microfluidic platform serves as an automated and highly integrated cell culture device for rapid, and real-time production of therapeutic exosomes that could advance cancer immunotherapy.

scholarly journals Lymphatic Control of the Tumor Immune Microenvironment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. SCI-46-SCI-46
Author(s):  
Melody A. Swartz
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Cancer Immunotherapy ◽  
T Cell Activation ◽  
Immune Suppression ◽  
Cell Activation ◽  
Conflicts Of Interest ◽  
Lymphatic Vessels ◽  
Cell Types

Tumor engagement or activation of surrounding lymphatic vessels is well-known to correlate with tumor progression and metastasis in melanoma and many other cancers. We and others have identified several mechanisms by which the lymphatic growth factor VEGF-C and lymphangiogenesis can promote metastasis, including (i) increasing immune suppressive cell types and factors in the tumor microenvironment both directly and indirectly, (ii) inhibiting maturation of antigen-presenting cells and T cell activation, and (iii) driving changes in the stromal microenvironment that promote both cancer invasion and immune suppression. However, lymphatic activation also enhances communication with cells in the draining lymph node by antigen and cell transport, which may trigger the initiation of adaptive immune responses against the tumor. Under normal conditions, the potential anti-tumor effects are rendered 'dormant' by the pro-tumor immune suppression, and the tumor progresses. However, we are now observing that lymphangiogenic tumors are exceptionally responsive to immunotherapy, implying that the anti-tumor aspects can be unleashed when the overall balance of pro- and anti-tumor immune aspects is tipped enough towards the latter (e.g., upon tumor cell killing). On the mechanistic side, we are finding that 'lymphangiogenic potentiation' depends on tumor cell infiltration of both CD103+ dendritic cells and naïve T cells, driving local T cell education post-immunotherapy and antigen spreading. On the translational side, we are developing novel strategies to exploit lymphangiogenesis for cancer immunotherapy. Understanding the yin and yang of lymphatic activation in the tumor microenvironment and how it affects immunity may lead to exciting new translational strategies for cancer immunotherapy. Disclosures No relevant conflicts of interest to declare.

VISTA inhibitors in cancer immunotherapy: a short perspective in recent progress

2021 ◽  
Author(s):  
Chenyang Wu ◽  
Xin Cao ◽  
xiaojin zhang
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Signaling Pathway ◽  
T Cell Activation ◽  
Recent Progress ◽  
Cell Activation ◽  
Cytokine Production ◽  
T Cell Proliferation

V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is a novel negative checkpoint regulator that mediates T cell proliferation and cytokine production. Blockade of the VISTA signaling pathway has...

scholarly journals Non-invasive biomarkers for monitoring the immunotherapeutic response to cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Sabah Nisar ◽  
Ajaz A. Bhat ◽  
Sheema Hashem ◽  
Santosh K. Yadav ◽  
Arshi Rizwan ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
T Cell Activation ◽  
Cell Activation ◽  
Imaging Techniques ◽  
T Cell Responses ◽  
Imaging Biomarkers ◽  
Non Invasive ◽  
Cell Responses ◽  
Recent Emergence

AbstractImmunotherapy is an efficient way to cure cancer by modulating the patient’s immune response. However, the immunotherapy response is heterogeneous and varies between individual patients and cancer subtypes, reinforcing the need for early benefit predictors. Evaluating the infiltration of immune cells in the tumor and changes in cell-intrinsic tumor characteristics provide potential response markers to treatment. However, this approach requires invasive sampling and may not be suitable for real-time monitoring of treatment response. The recent emergence of quantitative imaging biomarkers provides promising opportunities. In vivo imaging technologies that interrogate T cell responses, metabolic activities, and immune microenvironment could offer a powerful tool to monitor the cancer response to immunotherapy. Advances in imaging techniques to identify tumors' immunological characteristics can help stratify patients who are more likely to respond to immunotherapy. This review discusses the metabolic events that occur during T cell activation and differentiation, anti-cancer immunotherapy-induced T cell responses, focusing on non-invasive imaging techniques to monitor T cell metabolism in the search for novel biomarkers of response to cancer immunotherapy.

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