scholarly journals Bringing Macrophages to the Frontline against Cancer: Current Immunotherapies Targeting Macrophages

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2364
Author(s):  
Mariana Reis-Sobreiro ◽  
Afonso Teixeira da Mota ◽  
Carolina Jardim ◽  
Karine Serre
Keyword(s):  
T Cells ◽  
Cancer Progression ◽  
Tissue Repair ◽  
Antitumor Immunity ◽  
Therapeutic Potential ◽  
Adult Life ◽  
Clinical Results ◽  
Cancer Growth ◽  
Cancer Immunotherapies ◽  
Oncologic Diseases

Macrophages are found in all tissues and display outstanding functional diversity. From embryo to birth and throughout adult life, they play critical roles in development, homeostasis, tissue repair, immunity, and, importantly, in the control of cancer growth. In this review, we will briefly detail the multi-functional, protumoral, and antitumoral roles of macrophages in the tumor microenvironment. Our objective is to focus on the ever-growing therapeutic opportunities, with promising preclinical and clinical results developed in recent years, to modulate the contribution of macrophages in oncologic diseases. While the majority of cancer immunotherapies target T cells, we believe that macrophages have a promising therapeutic potential as tumoricidal effectors and in mobilizing their surroundings towards antitumor immunity to efficiently limit cancer progression.

Abstract B081: Tissue repair function of regulatory T cells during infection and cancer progression

2016 ◽  
Author(s):  
Wei Hu ◽  
Nicholas Arpaia ◽  
Paula D. Bos ◽  
Jesse Green ◽  
Alexander Rudensky
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cancer Progression ◽  
Tissue Repair

scholarly journals Potential Roles of Iridoid Glycosides and Their Underlying Mechanisms against Diverse Cancer Growth and Metastasis: Do They Have an Inhibitory Effect on Cancer Progression?

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2974
Author(s):  
Cho-Won Kim ◽  
Kyung-Chul Choi
Keyword(s):  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Iridoid Glycosides ◽  
Inhibitory Effect ◽  
Cancer Growth ◽  
Mesenchymal Transition ◽  
Cycle Arrest ◽  
Underlying Mechanisms ◽  
Cluster Of Differentiation

Iridoids are glycosides found in plants, having inherent roles in defending them against infection by viruses and microorganisms, and in the rapid repair of damaged areas. The emerging roles of iridoid glycosides on pharmacological properties have aroused the curiosity of many researchers, and studies undertaken indicate that iridoid glycosides exert inhibitory effects in numerous cancers. This review focuses on the roles and the potential mechanism of iridoid glycosides at each stage of cancer development such as proliferation, epithelial mesenchymal transition (EMT), migration, invasion and angiogenesis. Overall, the reviewed literature indicates that iridoid glycosides inhibit cancer growth by inducing cell cycle arrest or by regulating apoptosis-related signaling pathways. In addition, iridoid glycosides suppress the expression and activity of matrix metalloproteinases (MMPs), resulting in reduced cancer cell migration and invasiveness. The antiangiogenic mechanism of iridoid glycosides was found to be closely related to the transcriptional regulation of pro-angiogenic factors, i.e., vascular endothelial growth factors (VEGFs) and cluster of differentiation 31 (CD31). Taken together, these results indicate the therapeutic potential of iridoid glycosides to alleviate or prevent rapid cancer progression and metastasis.

scholarly journals Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion

Blood ◽  
2009 ◽  
Vol 114 (16) ◽  
pp. 3431-3438 ◽  
Author(s):  
Roch Houot ◽  
Matthew J. Goldstein ◽  
Holbrook E. Kohrt ◽  
June H. Myklebust ◽  
Ash A. Alizadeh ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
T Cells ◽  
Antitumor Immunity ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Adaptive Immune Response ◽  
Primary Lymphoma ◽  
Treg Depletion

Abstract Despite the success of passive immunotherapy with monoclonal antibodies (mAbs), many lymphoma patients eventually relapse. Induction of an adaptive immune response may elicit active and long-lasting antitumor immunity, thereby preventing or delaying recurrence. Immunomodulating mAbs directed against immune cell targets can be used to enhance the immune response to achieve efficient antitumor immunity. Anti-CD137 agonistic mAb has demonstrated antitumor efficacy in various tumor models and has now entered clinical trials for the treatment of solid tumors. Here, we investigate the therapeutic potential of anti-CD137 mAb in lymphoma. We found that human primary lymphoma tumors are infiltrated with CD137+ T cells. We therefore hypothesized that lymphoma would be susceptible to treatment with anti-CD137 agonistic mAb. Using a mouse model, we demonstrate that anti-CD137 therapy has potent antilymphoma activity in vivo. The antitumor effect of anti-CD137 therapy was mediated by both natural killer (NK) and CD8 T cells and induced long-lasting immunity. Moreover, the antitumor activity of anti-CD137 mAb could be further enhanced by depletion of regulatory T cell (Tregs). These results support the evaluation of anti-CD137 therapy in clinical trials for patients with lymphoma.

scholarly journals Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia

Blood ◽  
2012 ◽  
Vol 120 (12) ◽  
pp. 2417-2427 ◽  
Author(s):  
Junko Baba ◽  
Satoshi Watanabe ◽  
Yu Saida ◽  
Tomohiro Tanaka ◽  
Takao Miyabayashi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Antitumor Immunity ◽  
Suppressor Cells ◽  
Whole Body ◽  
Antitumor Effects ◽  
Treg Depletion ◽  
Antitumor Effector ◽  
Cytotoxic Therapies ◽  
Cancer Immunotherapies

Abstract Cytotoxic lymphodepletion therapies augment antitumor immune responses. The generation and therapeutic efficacy of antitumor effector T cells (TEs) are enhanced during recovery from lymphopenia. Although the effects of lymphodepletion on naive T cells (TNs) and TEs have been studied extensively, the influence of lymphodepletion on suppressor cells remains poorly understood. In this study, we demonstrate a significant increase of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in sublethally irradiated lymphopenic mice. These radio-resistant Tregs inhibited the induction of TEs in tumor-draining lymph-nodes (TDLNs) during recovery from lymphopenia. The transfer of TNs into lymphopenic tumor-bearing mice resulted in some antitumor effects; however, Treg depletion after whole-body irradiation and reconstitution strongly inhibited tumor progression. Further analyses revealed that tumor-specific T cells were primed from the transferred TNs, whereas the Tregs originated from irradiated recipient cells. As in irradiated lymphopenic mice, a high percentage of Tregs was observed in cyclophosphamide-treated lymphopenic mice. The inhibition of Tregs in cyclophosphamide-treated mice significantly reduced tumor growth. These results indicate that the Tregs that survive cytotoxic therapies suppress antitumor immunity during recovery from lymphopenia and suggest that approaches to deplete radio and chemo-resistant Tregs can enhance cancer immunotherapies.

scholarly journals 10.03 Interleukin-22 regulates anti-tumor immunity in mouse models of lung and breast carcinoma

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A2.1-A2
Author(s):  
D Briukhovetska ◽  
J Suarez-Gosalvez ◽  
M Schübel ◽  
A Markota ◽  
J Jobst ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Tumor Cells ◽  
Mouse Models ◽  
Cancer Progression ◽  
Antitumor Immunity ◽  
Cytotoxic T Cells ◽  
Metastatic Breast ◽  
Interleukin 22 ◽  
Natural Regulation

BackgroundHigh expression of CD155 (poliovirus receptor, PVR) is associated with a poor prognosis of lung adenocarcinoma (LUAD) and triple-negative breast cancer (TNBC) patients. When overexpressed, this molecule inhibits the antitumor function of NK and cytotoxic T cells through binding to its inhibitory co-receptors TIGIT and CD96, and downregulation of stimulatory CD226 (DNAM-1). However, the exact mechanism of CD155 overexpression on the tumor cells remains unclear. Here we demonstrate that interleukin-22 (IL-22), a cytokine known to promote cancer progression, induces upregulation of CD155 on tumor cells in mouse models of breast and lung cancer and may, thus, inhibit antitumor immunity and promote lung metastasis.Materials and MethodsTo study the influence of IL-22 on antitumor immunity, we utilize IL-22-deficient animals in syngeneic mouse models of metastatic breast and lung cancer. For this purpose, we generated tumor cells deficient in IL-22 receptor (IL-22R) or in CD155 and tumor cells, that constantly express CD155 independent of its natural regulation. Here, we determine the incidence of metastasis and antitumor NK and T cell responses in the lung, the primary site of metastasis.ResultsWe demonstrate that murine cancer cells upregulate CD155 surface expression upon treatment with recombinant IL-22, whereas this effect is abolished in the absence of IL-22R. Furthermore, IL-22-deficient animals have a lower metastatic burden in the lung and demonstrate a dramatic increase in IFN-γ production in NK, and, to a lower extent, cytotoxic T cells. Moreover, this effect is reversed when CD155 is expressed on the tumor cells independent of its natural regulation, which enables lung metastases in IL-22 deficient animals. Phenotypically, NK cells in IL-22 knockout mice have a higher expression of co-stimulatory receptor CD226, which is linked to the antitumor potential of these cells.ConclusionsHere we demonstrate a novel pathway of cytokine-mediated cancer progression, where IL-22 is capable of inducing CD155 on the tumor cells and, therefore, promotes an immunosuppressive tumor microenvironment. This highlights the potential of IL-22 as a target for immunotherapy considering the complexity of the CD155-dependent immunoregulatory network.Disclosure InformationD. Briukhovetska: None. J. Suarez-Gosalvez: None. M. Schübel: None. A. Markota: None. J. Jobst: None. J. Dörr: None. F. Märkl: None. M. Schwerdtfeger: None. A. Öner: None. M. Seifert: None. A. Gottschlich: None. S. Endres: None. S. Kobold: None.

Effect of Lymphodepletion on Donor T Cells and the Role of Recipient Cells Persisting after Cytotoxic Treatments in Cancer Immunotherapies

2017 ◽  
Vol 37 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Satoshi Watanabe ◽  
Masashi Arita ◽  
Miho Takahashi ◽  
Yu Saida ◽  
Toshiyuki Koya ◽  
...  
Keyword(s):  
T Cells ◽  
Donor T Cells ◽  
Cancer Immunotherapies

scholarly journals Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

2017 ◽  
Vol 24 (10) ◽  
pp. R349-R366 ◽  
Author(s):  
Catherine Zabkiewicz ◽  
Jeyna Resaul ◽  
Rachel Hargest ◽  
Wen Guo Jiang ◽  
Lin Ye
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Bone Morphogenetic Proteins ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Breast Tumour ◽  
Cellular Functions ◽  
Foetal Development ◽  
Key Factor ◽  
The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

scholarly journals DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

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