scholarly journals Nanoparticles Targeting Innate Immune Cells in Tumor Microenvironment

2021 ◽  
Vol 22 (18) ◽  
pp. 10009
Author(s):  
Hochung Jang ◽  
Eun Hye Kim ◽  
Sung-Gil Chi ◽  
Sun Hwa Kim ◽  
Yoosoo Yang
Keyword(s):  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Suppressor Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Microenvironments ◽  
Clinical Benefits

A variety of innate immune cells such as macrophages, dendritic cells, myeloid-derived suppressor cells, natural killer cells, and neutrophils in the tumor microenvironments, contribute to tumor progression. However, while several recent reports have studied the use of immune checkpoint-based cancer immunotherapy, little work has focused on modulating the innate immune cells. This review focuses on the recent studies and challenges of using nanoparticles to target innate immune cells. In particular, we also examine the immunosuppressive properties of certain innate immune cells that limit clinical benefits. Understanding the cross-talk between tumors and innate immune cells could contribute to the development of strategies for manipulating the nanoparticles targeting tumor microenvironments.

scholarly journals Anti-Tumor Effects of Chinese Medicine Compounds by Regulating Immune Cells in Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Fengqian Chen ◽  
Jingquan Li ◽  
Hui Wang ◽  
Qian Ba
Keyword(s):  
Dendritic Cells ◽  
Chinese Medicine ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Traditional Chinese Medicine ◽  
Tumor Cells ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Adaptive Immune Cells

As the main cause of death in the world, cancer is one of the major health threats for humans. In recent years, traditional Chinese medicine has gained great attention in oncology due to the features of multi-targets, multi-pathways, and slight side effects. Moreover, lots of traditional Chinese medicine can exert immunomodulatory effects in vivo. In the tumor microenvironment, tumor cells, immune cells as well as other stromal cells often coexist. With the development of cancer, tumor cells proliferate uncontrollably, metastasize aggressively, and modulate the proportion and status of immune cells to debilitate the antitumor immunity. Reversal of immunosuppressive tumor microenvironment plays an essential role in cancer prevention and therapy. Immunotherapy has become the most promising strategy for cancer therapy. Chinese medicine compounds can stimulate the activation and function of immune cells, such as promoting the maturation of dendritic cells and inducing the differentiation of myeloid-derived suppressor cells to dendritic cells and macrophages. In the present review, we summarize and discuss the effects of Chinese medicine compounds on immune cells in the tumor microenvironment, including innate immune cells (dendritic cells, natural killer cells, macrophages, and myeloid-derived suppressor cells) and adaptive immune cells (CD4+/CD8+ T lymphocytes and regulatory T cells), and the various immunomodulatory roles of Chinese medicine compounds in cancer therapy such as improving tumor-derived inflammation, enhancing the immunity after surgery or chemotherapy, blocking the immune checkpoints, et al., aiming to provide more thoughts for the anti-tumor mechanisms and applications of Chinese medicine compounds in terms of tumor immunity.

scholarly journals Terminating Cancer by Blocking VISTA as a Novel Immunotherapy: Hasta la vista, baby

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji-Eun Irene Yum ◽  
Young-Kwon Hong
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Checkpoint Molecule

VISTA is an up-and-coming immune checkpoint molecule that can become the target of new cancer immunotherapy treatments. Immune cells in the tumor microenvironment can largely influence the progression of cancer through inhibitory and stimulatory pathways. Indeed, VISTA is expressed on many immune cells, including T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and dendritic cells. VISTA has predominantly been shown to act in an immune-suppressing manner that enables cancer progression. This review will delve into results from preclinical murine studies of anti-VISTA monoclonal antibody treatments, bring together recent studies that detect VISTA expression on immune cells from patient tumors of various cancers, and discuss ongoing clinical trials involving VISTA.

scholarly journals The effect of PEGylation on the efficacy and uptake of an immunostimulatory nanoparticle in the tumor immune microenvironment

2021 ◽  
Author(s):  
Wyatt M. Becicka ◽  
Peter Bielecki ◽  
Morgan Lorkowski ◽  
Taylor J. Moon ◽  
Yahan Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Immunosuppressive Tumor Microenvironment

The efficacy of immunotherapies is often limited by the immunosuppressive tumor microenvironment, which is populated with dysfunctional innate immune cells. To reprogram the tumor-resident innate immune cells, we developed an...

scholarly journals Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 456 ◽  
Author(s):  
Philippe Saas ◽  
Alexis Varin ◽  
Sylvain Perruche ◽  
Adam Ceroi
Keyword(s):  
Dendritic Cells ◽  
Lipid Metabolism ◽  
Nuclear Receptors ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Plasmacytoid Dendritic Cell ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Cells ◽  
Immune Functions

There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

scholarly journals IMMU-39. RNA LOADED LIPID-NANOPARTICLES FUNCTION AS CUSTOMIZABLE IMMUNOTHERAPEUTIC VEHICLES AGAINST MALIGNANT GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi127-vi127
Author(s):  
Adam Grippin ◽  
Brandon Wummer ◽  
Hector Mendez-Gomez ◽  
Brian Stover ◽  
Jianping Huang ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Lipid Nanoparticles ◽  
Lymphoid Organs ◽  
Innate Immune ◽  
T Cell Immunity ◽  
Innate Immune Cells ◽  
Cell Immunity ◽  
The Brain

Abstract BACKGROUND While dendritic cell (DC) vaccine therapy has shown considerable promise for glioblastoma (GBM) patients (Mitchell et al. Nature, 2015), their advancement into human clinical trials has been fraught with challenges in the development, manufacturing, and marketing of successful cancer immunotherapies. To circumvent the challenges associated with cell therapy, we have developed a new platform technology consisting of tumor derived mRNA complexed into lipid-nanoparticles (RNA-NPs) for systemic delivery to DCs in vivo and induction of antigen specific T cell immunity against GBM. OBJECTIVES/ METHODS We sought to assess if surface and charge modifications to our custom lipid-NP could facilitate its localization to lymphoid organs and the brain tumor microenvironment. RESULTS We demonstrate that intravenous administration of our unmodified custom RNA-NPs mediate systemic activation of DCs; these include activation of CD11c+ cells in the brains of animals with intact blood brain-barriers (BBBs). RNA-NPs mediate antigen specific T cell immunity and anti-tumor efficacy with increased tumor infiltrating lymphocytes against a NF-1/p53 mutant glioma that recapitulates features of human GBM in immunocompetent mice. Modification of surface charge could direct these RNA-NPs to lymphoid organs (e.g. spleen, lymph nodes) while modification of the lipid backbone (with cholesterol) enhances localization to innate immune cells in NF-1/p53 mutant and GL261 gliomas. We therefore assessed if this customizable lipid-NP could be leveraged for delivery of immune checkpoint inhibitors (ICIs) (i.e. PD-L1 siRNA) to the brain tumor microenvironment. Compared with scrambled siRNA-NPs in combination with ICIs, surface modified siRNA-NPs (antagonizing PD-L1) in combination with ICIs mediated significant antitumor efficacy with 37% long term survivors in an otherwise fatal brain tumor model. CONCLUSION We designed multifunctional RNA-NPs with a simple, scalable synthesis method that enables delivery of nucleic acids to innate immune cells in lymphoid organs and brain tumors.

scholarly journals Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1411 ◽  
Author(s):  
Irina Larionova ◽  
Elena Kazakova ◽  
Marina Patysheva ◽  
Julia Kzhyshkowska
Keyword(s):  
Fatty Acid ◽  
Immune Cells ◽  
Tumor Response ◽  
Macrophage Polarization ◽  
Innate Immune ◽  
Acid Oxidation ◽  
Innate Immune Cells ◽  
Primary Tumor Growth ◽  
Tumor Microenvironments ◽  
Functional Polarization

Macrophages are key innate immune cells in the tumor microenvironment (TME) that regulate primary tumor growth, vascularization, metastatic spread and tumor response to various types of therapies. The present review highlights the mechanisms of macrophage programming in tumor microenvironments that act on the transcriptional, epigenetic and metabolic levels. We summarize the latest knowledge on the types of transcriptional factors and epigenetic enzymes that control the direction of macrophage functional polarization and their pro- and anti-tumor activities. We also focus on the major types of metabolic programs of macrophages (glycolysis and fatty acid oxidation), and their interaction with cancer cells and complex TME. We have discussed how the regulation of macrophage polarization on the transcriptional, epigenetic and metabolic levels can be used for the efficient therapeutic manipulation of macrophage functions in cancer.

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

Calreticulin Promotes Immunity Against Acute Myeloid Leukemia Cells in Vivo

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 996-996
Author(s):  
Xiufen Chen ◽  
Dominick Fosco ◽  
Douglas E. Kline ◽  
Justin Kline
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Surface ◽  
Vector Control ◽  
Immune Cells ◽  
Myeloid Leukemia ◽  
Innate Immune ◽  
Innate Immune Cells

Abstract Pre-apoptotic cancer cells release internalized calreticulin (CRT) to their surface prior to death, which acts as an ‘eat-me’ signal to local phagocytes. Chemotherapy and irradiation, which can induce immunogenic cell death through CRT translocation, can also result in local and/or systemic immune suppression in the host. To bypass the requirement of exposing the host to chemotherapy to induce translocation of CRT to the cell surface, murine acute myeloid leukemia (AML) cells (C1498), were engineered to constitutively express cell surface CRT (C1498.CRT). Vector control C1498 or C1498.CRT cells were inoculated intravenously (IV) into C57BL/6 mice. Significantly prolonged survival was observed in hosts harboring C1498.CRT versus vector control C1498 cells systemically. The survival benefit were abrogated in both Rag2-/- hosts or by depletion of T cells with anti-CD4 plus anti-CD8 antibodies, arguing that the immune-mediated effect of cell-surface CRT expression is dependent upon a functional adaptive immune system. More strikingly, systemic inoculation with C1498.CRT cells expressing the model SIYRYYGL (SIY) peptide antigen (C1498.SIY.CRT cells) resulted in almost complete protection from AML development (>90% long term survival vs. 10% of C1498.SIY vector control cells). All animals surviving a primary C1498.SIY.CRT challenge rejected a subsequent re-challenge with C1498.SIY cells, suggesting that CRT-expressing AML cells promote immunologic memory. Significantly enhanced expansion and unregulated IFNγ production were observed among SIY-specific T cell receptor transgenic CD8+ 2C T cells following their adoptive transfer into hosts bearing C1498.SIY.CRT AML cells versus vector control C1498.SIY cells. Interestingly, CRT expression on AML cells did not promote their in vivo phagocytosis by innate immune cells, specifically splenic CD8a+ dendritic cells known to engulf AML cells following their IV inoculation. IL-12 production by CD8α+CD11c+ dendritic cells which had engulfed C1498 and C1498.CRT cells in vivo was similarly induced, and cross-presentation of the SIY antigen to 2C T cells ex vivo by purified CD8a+DCs following in vivo exposure to C1498.SIY or C1498.SIY.CRT cells was also similar. In conclusion, it is clear that expression on CRT on the surface of AML cells leads to robust leukemia-specific T cell activation and expansion resulting in prolonged leukemia-specific survival in AML-bearing animals. Although a direct effect of CRT on innate immune cells, such as dendritic cells, is suspected, the molecular mechanism underlying the “CRT effect” remains unclear, and is being explored further through gene expression analysis in purified DCs which have engulfed CRT-expressing or control AML cells in vivo, as well as in animals genetically deficient in the putative CRT receptor, LRP, in dendritic cells. It will be of interest to analyze spontaneous CRT expression on AML cells from human samples and to correlate cell surface CRT expression with the presence or absence of spontaneous T cell responses to known AML antigens and with clinical outcomes. Disclosures No relevant conflicts of interest to declare.

scholarly journals Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic melanoma

2018 ◽  
Author(s):  
Carlos R. Figueiredo ◽  
Ricardo A. Azevedo ◽  
Sasha Mousdell ◽  
Pedro T. Resende-Lara ◽  
Lucy Ireland ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Metastatic Melanoma ◽  
Immune Cells ◽  
Tumour Microenvironment ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Adaptive Immune Cells ◽  
Cancer Immunotherapies

ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in metastatic melanoma. The Ig-CDR-based peptide C36L1 is able to restore macrophages and dendritic cells’ immunogenic functions and to inhibit metastatic growth in vivo. Mechanistically, we found that C36L1 interferes with the MIF-CD74 tumour-innate immune cells immunosuppressive signalling pathway and thereby restores an effective anti-tumour immune response. C36L1 directly binds to CD74 on macrophages and dendritic cells, disturbing CD74 structural dynamics and inhibiting MIF signalling through CD74. Our findings suggest that interfering with MIF-CD74 immunosuppressive signalling in macrophages and dendritic cells using peptide-based immunotherapy can restore the anti-tumour immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the anti-tumour immune response.

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