scholarly journals The Role of Chemoattractant Receptors in Shaping the Tumor Microenvironment

2014 ◽  
Vol 2014 ◽  
pp. 1-33 ◽  
Author(s):  
Jiamin Zhou ◽  
Yi Xiang ◽  
Teizo Yoshimura ◽  
Keqiang Chen ◽  
Wanghua Gong ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immune Cells ◽  
Malignant Tumors ◽  
G Protein Coupled Receptors ◽  
Host Cells ◽  
The Past ◽  
G Protein Coupled

Chemoattractant receptors are a family of seven transmembrane G protein coupled receptors (GPCRs) initially found to mediate the chemotaxis and activation of immune cells. During the past decades, the functions of these GPCRs have been discovered to not only regulate leukocyte trafficking and promote immune responses, but also play important roles in homeostasis, development, angiogenesis, and tumor progression. Accumulating evidence indicates that chemoattractant GPCRs and their ligands promote the progression of malignant tumors based on their capacity to orchestrate the infiltration of the tumor microenvironment by immune cells, endothelial cells, fibroblasts, and mesenchymal cells. This facilitates the interaction of tumor cells with host cells, tumor cells with tumor cells, and host cells with host cells to provide a basis for the expansion of established tumors and development of distant metastasis. In addition, many malignant tumors of the nonhematopoietic origin express multiple chemoattractant GPCRs that increase the invasiveness and metastasis of tumor cells. Therefore, GPCRs and their ligands constitute targets for the development of novel antitumor therapeutics.

scholarly journals The Role of TRAIL/DRs in the Modulation of Immune Cells and Responses

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1469 ◽  
Author(s):  
Duygu Sag ◽  
Zeynep Ozge Ayyildiz ◽  
Sinem Gunalp ◽  
Gerhard Wingender
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Necrosis Factor ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Necrosis ◽  
Death Receptors ◽  
Induction Of Apoptosis ◽  
Necrosis Factor

Expression of TRAIL (tumor necrosis factor–related apoptosis–inducing ligand) by immune cells can lead to the induction of apoptosis in tumor cells. However, it becomes increasingly clear that the interaction of TRAIL and its death receptors (DRs) can also directly impact immune cells and influence immune responses. Here, we review what is known about the role of TRAIL/DRs in immune cells and immune responses in general and in the tumor microenvironment in particular.

scholarly journals Inflammatory Cells in Diffuse Large B Cell Lymphoma

2020 ◽  
Vol 9 (8) ◽  
pp. 2418
Author(s):  
Roberto Tamma ◽  
Girolamo Ranieri ◽  
Giuseppe Ingravallo ◽  
Tiziana Annese ◽  
Angela Oranger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells.

scholarly journals MicroRNAs: immune modulators in cancer immunotherapy

2021 ◽  
Author(s):  
Yun Xing ◽  
Zhiqiang Wang ◽  
Zhou Lu ◽  
Jie Xia ◽  
Zhangjuan Xie ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Tumor Suppressors ◽  
Immune Modulators ◽  
Non Coding Rna ◽  
New Findings

Abstract MicroRNA (miRNA) is a class of endogenous small non-coding RNA of 18–25 nucleotides and plays regulatory roles in both physiological and pathological processes. Emerging evidence support that miRNAs function as immune modulators in tumors. MiRNAs as tumor suppressors or oncogenes are also found to be able to modulate anti-tumor immunity or link the crosstalk between tumor cells and immune cells surrounding. Based on the specific regulating function, miRNAs can be used as predictive, prognostic biomarkers and therapeutic targets in immunotherapy. Here, we review new findings about role of miRNAs in modulating immune responses, as well as discuss mechanisms underlying their dysregulation, and their clinical potentials as indicators of tumor prognosis or to sensitize cancer immunotherapy.

scholarly journals The Role of Interleukin-33 in Head and Neck Squamous Cell Carcinoma Is Determined by Its Cellular Sources in the Tumor Microenvironment

2021 ◽  
Vol 10 ◽  
Author(s):  
Liang Peng ◽  
Wei Sun ◽  
Lin Chen ◽  
Wei-Ping Wen
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Rna Seq ◽  
Interleukin 33

ObjectivesTo investigate the role of interleukin-33 (IL-33) in head and neck squamous cell carcinoma (HNSCC).Materials and MethodsRNA-seq data of 520 cases of HNSCC were retrieved from The Cancer Genome Atlas. The tumor microenvironment was deconstructed by xCell using bulk RNA-seq data. The cohort was dichotomized by the median IL-33 expression level. Immune cell components and molecular markers were compared between the high and low IL-33 groups. The prognostic value of IL-33 was evaluated by the log-rank test. Differential gene expression analysis and KEGG pathway enrichment analysis were also conducted. The relationship between the IL-33 expression level and the abundance of its potential cellular sources was evaluated by Pearson’s partial correlation test. Subgroup analysis was conducted in laryngeal, oropharyngeal, and oral cavity squamous cell carcinoma (LSCC, OPSCC, and OCSCC).ResultsThe role of IL-33 in HNSCC was heterogeneous among tumors at different sites. In LSCC, IL-33 may increase the extent of malignancy of tumor cells and act as a pro-tumor factor. In OCSCC, IL-33 may play a role in orchestrating the immune responses against tumor cells and act as an antitumor factor. The role of IL-33 in OPSCC was undetermined. IL-33 in LSCC was mainly derived from endothelial cells, while IL-33 in OCSCC was mainly derived from endothelial and epithelial cells.ConclusionAccording to the different sources of IL-33 in LSCC and OCSCC, we propose a hypothesis that stroma-derived IL-33 could favor tumor progression, while epithelial-derived IL-33 could favor antitumor immune responses in HNSCC.

Mesenchymal Stem Cells, Immune Cells and Tumor Cells Crosstalk: A Sinister Triangle in the Tumor Microenvironment

2019 ◽  
Vol 14 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Mahboobeh Razmkhah ◽  
Shabnam Abtahi ◽  
Abbas Ghaderi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immune Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Mesenchymal Stem Cells [MSCs] are a heterogeneous population of fibroblast-like cells which maintain self-renewability and pluripotency. Many studies have demonstrated the immunomodulatory effects of MSCs on the innate and adaptive immune cells. As a result of interactions with tumor cells, microenvironment and immune-stimulating milieu, MSCs contribute to tumor progression by several mechanisms, including sustained proliferative signal in cancer stem cells [CSCs], inhibition of tumor cell apoptosis, transition to tumor-associated fibroblasts [TAFs], promotion of angiogenesis, stimulation of epithelial-mesenchymal transition [EMT], suppression of immune responses, and consequential promotion of tumor metastasis. Here, we present an overview of the latest findings on Janusfaced roles that MSCs play in the tumor microenvironment [TME], with a concise focus on innate and adaptive immune responses.

scholarly journals Role of KNDy Neurons Expressing Kisspeptin, Neurokinin B, and Dynorphin A as a GnRH Pulse Generator Controlling Mammalian Reproduction

2021 ◽  
Vol 12 ◽  
Author(s):  
Yoshihisa Uenoyama ◽  
Mayuko Nagae ◽  
Hitomi Tsuchida ◽  
Naoko Inoue ◽  
Hiroko Tsukamura
Keyword(s):  
Pulse Generator ◽  
Pulse Generation ◽  
G Protein Coupled Receptors ◽  
Historical Background ◽  
Dynorphin A ◽  
Neurokinin B ◽  
The Past ◽  
Kndy Neurons ◽  
G Protein Coupled

Increasing evidence accumulated during the past two decades has demonstrated that the then-novel kisspeptin, which was discovered in 2001, the known neuropeptides neurokinin B and dynorphin A, which were discovered in 1983 and 1979, respectively, and their G-protein-coupled receptors, serve as key molecules that control reproduction in mammals. The present review provides a brief historical background and a summary of our recent understanding of the roles of hypothalamic neurons expressing kisspeptin, neurokinin B, and dynorphin A, referred to as KNDy neurons, in the central mechanism underlying gonadotropin-releasing hormone (GnRH) pulse generation and subsequent tonic gonadotropin release that controls mammalian reproduction.

Monocytes in the Tumor Microenvironment

2021 ◽  
Vol 16 (1) ◽  
pp. 93-122
Author(s):  
Stefano Ugel ◽  
Stefania Canè ◽  
Francesco De Sanctis ◽  
Vincenzo Bronte
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Tumor Cells ◽  
Current Knowledge ◽  
Tumor Development ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
The Past ◽  
Immunosuppressive Tumor Microenvironment ◽  
Antigen Presenting

Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various mechanisms that induce immune tolerance, angiogenesis, and increased dissemination of tumor cells. Yet monocytes can also give rise to antitumor effectors and activate antigen-presenting cells. This yin-yang activity relies on the plasticity of monocytes in response to environmental stimuli. In this review, we summarize current knowledge of the ontogeny, heterogeneity, and functions of monocytes and monocyte-derived cells in cancer, pinpointing the main pathways that are important for modeling the immunosuppressive tumor microenvironment.

Role of Tumor Microenvironment in Cancer Stem Cells Resistance to Radiotherapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Shahram Taeb ◽  
Milad Ashrafizadeh ◽  
Ali Zarrabi ◽  
Saeed Rezapoor ◽  
Ahmed Eleojo Musa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Stromal Cells ◽  
Hypoxia Inducible Factor ◽  
Proliferation Capacity ◽  
Chronic Disorder

Abstract: Cancer is a chronic disorder that involves several elements of both the tumor and the host stromal cells. At present, the complex relationship between the various factors presents in the tumor microenvironment (TME) and tumor cells, as well as immune cells located within the TME, is still poorly known. Within the TME, the crosstalk of these factors and immune cells essentially determines how a tumor reacts to the treatment and how the tumor can ultimately be destroyed, remain dormant, or develop and metastasize. Also, in TME, reciprocal crosstalk between cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), hypoxia-inducible factor (HIF) intensifies the proliferation capacity of cancer stem cells (CSCs). CSCs are subpopulation of cells that reside within the tumor bulk and have the capacity to self-renew, differentiate, and repair DNA damage. These characteristics make CSCs develop resistance to a variety of treatments, such as radiotherapy (RT). RT is a frequent and often curative treatment for local cancer which mediates tumor elimination by cytotoxic actions. Also, cytokines and growth factors that are released into TME, have been involved in the activation of tumor radioresistance and the induction of different immune cells, altering local immune responses. In this review, we discuss the pivotal role of TME in resistance of CSCs to RT.

scholarly journals Knockout of High-Mobility Group Box 1 in B16F10 Melanoma Cells Induced Host Immunity-Mediated Suppression of In Vivo Tumor Growth

2021 ◽  
Author(s):  
Kanako Yokomizo ◽  
Kayoko Waki ◽  
Miyako Ozawa ◽  
Keiko Yamamoto ◽  
Sachiko Ogasawara ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
High Mobility

Abstract High mobility group box 1 (HMGB1) has been reported as a damage-associated molecular pattern (DAMP) molecule that is released from damaged or dead cells and induces inflammation and subsequent innate immunity. However, the role of HMGB1 in the anti-tumor immunity is unclear since inflammation in the tumor microenvironment also contributes to tumor promotion and progression. In the present study, we established HMGB1-knockout clones from B16F10 and CT26 murine tumors by genome editing using the CRISPR/Cas9 system and investigated the role of HMGB1 in anti-tumor immunity. We found that 1) knockout of HMGB1 in the tumor cells suppressed in vivo, but not in vitro, tumor growth, 2) the suppression of the in vivo tumor growth was mediated by CD8 T cells, and 3) infiltration of CD8 T cells, macrophages and dendritic cells into the tumor tissues was accelerated in HMGB1-knockout tumors. These results demonstrated that knockout of HMGB1 in tumor cells converted tumors from poor infiltration of immune cells called “cold” to “immune-inflamed” or “hot” and inhibited in vivo tumor growth mediated by cytotoxic T lymphocytes. Infiltration of immune cells to the tumor microenvironment is an important step in the series known as the cancer immunity cycle. Thus, manipulation of tumor-derived HMGB1 might be applicable to improve the clinical outcomes of cancer immunotherapies, including immune checkpoint blockades and cancer vaccine therapies.

scholarly journals Modulation of Tumor-Associated Macrophages (TAM) Phenotype by Platelet-Activating Factor (PAF) Receptor

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ildefonso Alves da Silva Junior ◽  
Simone Cardozo Stone ◽  
Renata Marques Rossetti ◽  
Sonia Jancar ◽  
Ana Paula Lepique
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Biological Effects ◽  
Platelet Activating Factor ◽  
Host Cells ◽  
Leukocyte Infiltration ◽  
Wild Type ◽  
B16f10 Melanoma ◽  
Paf Receptor

Platelet-activating factor (PAF) plays an important role in the pathogenesis of several types of tumors. The biological effects of PAF are mediated by the PAF receptor (PAFR), which can be expressed by tumor cells and host cells that infiltrate the tumor microenvironment. In the present study, we investigated the role of PAFR expressed by leukocytes that infiltrate two types of tumors, one that expresses PAFR (TC-1 carcinoma) and another that does not express the receptor (B16F10 melanoma) implanted in mice that express the receptor or not (PAFR KO). It was found that both tumors grew significantly less in PAFR KO than inwild-type(WT) mice. Analysis of the leukocyte infiltration shown in PAFR KO increased the frequency of neutrophils (Gr1+) and of CD8+lymphocytes in B16F10 tumors and of CD4+lymphocytes in TC-1 tumors. PAFR KO also had a higher frequency of M1-like (CD11c+) and lower M2-like (CD206+) macrophages infiltrated in both tumors. This was confirmed in macrophages isolated from the tumors that showed higher iNOS, lower arginase activity, and lower IL10 expression in PAFR KO tumors than WT mice. These data suggest that in the tumor microenvironment, endogenous PAF-like activity molecules bind PAFR in macrophages which acquire an M2-like profile and this promotes tumor growth.

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