scholarly journals The IL4I1 Enzyme: A New Player in the Immunosuppressive Tumor Microenvironment

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 757 ◽  
Author(s):  
Valérie Molinier-Frenkel ◽  
Armelle Prévost-Blondel ◽  
Flavia Castellano
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Essential Amino Acids ◽  
T Helper ◽  
Preclinical Models ◽  
Adaptive Immune ◽  
Immunosuppressive Tumor Microenvironment ◽  
Fine Control ◽  
Antigen Presenting

The high metabolic needs of T lymphocytes in response to activation make them particularly vulnerable to modifications of their biochemical milieu. Immunosuppressive enzymes produced in the tumor microenvironment modify nutrient availability by catabolizing essential or semi-essential amino acids and producing toxic catabolites, thus participating in the local sabotage of the antitumor immune response. L-amino-acid oxidases are FAD-bound enzymes found throughout evolution, from bacteria to mammals, and are often endowed with anti-infectious properties. IL4I1 is a secreted L-phenylalanine oxidase mainly produced by inflammatory antigen-presenting cells—in particular, macrophages present in T helper type 1 granulomas and in various types of tumors. In the last decade, it has been shown that IL4I1 is involved in the fine control of B- and T-cell adaptive immune responses. Preclinical models have revealed its role in cancer immune evasion. Recent clinical data highlight IL4I1 as a new potential prognostic marker in human melanoma. As a secreted enzyme, IL4I1 may represent an easily targetable molecule for cancer immunotherapy.

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.

Chemokines and dendritic cells in inflammatory myopathies: Figure 1

2009 ◽  
Vol 68 (3) ◽  
pp. 300-304 ◽  
Author(s):  
A Tournadre ◽  
P Miossec
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Inflammatory Myopathies ◽  
T Helper ◽  
Adaptive Immune ◽  
Antigen Presenting ◽  
Leucocyte Recruitment

This review focuses on the contribution of the local production of chemokines and cytokines and of dendritic cells (DC) to the pathogenesis of inflammatory myopathies. DC are the most efficient professional antigen-presenting cells (APC), which are critical for the development of innate and adaptive immune responses. Chemokines are important mediators of the immune response as they regulate leucocyte recruitment to tissue and play a key role in inflammatory diseases by acting on T-cell and DC migration. Recent advances indicate that the muscle cell itself could participate in the inflammatory process. Furthermore, the T-helper (Th) type 1 and Th17 proinflammatory cytokines, present in myositis samples, are associated with the migration, differentiation and maturation of inflammatory cells and allow a network of interactions between all the components of the immune response. An understanding of such interactions is essential because it can lead to therapeutic applications.

scholarly journals A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses

2007 ◽  
Vol 204 (12) ◽  
pp. 2963-2976 ◽  
Author(s):  
Koichiro Takahashi ◽  
Takuma Shibata ◽  
Sachiko Akashi-Takamura ◽  
Takashi Kiyokawa ◽  
Yasutaka Wakabayashi ◽  
...  
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Poly I:C ◽  
Toll Like Receptor ◽  
T Helper ◽  
Surface Molecules ◽  
Adaptive Immune ◽  
And Function ◽  
Tlr3 Ligand Poly

Immune cells express multiple Toll-like receptors (TLRs) that are concomitantly activated by a variety of pathogen products. Although there is presumably a need to coordinate the expression and function of TLRs in individual cells, little is known about the mechanisms governing this process. We show that a protein associated with TLR4 (PRAT4A) is required for multiple TLR responses. PRAT4A resides in the endoplasmic reticulum, and PRAT4A knockdown inhibited trafficking of TLR1 and TLR4 to the cell surface and ligand-induced trafficking of TLR9 to lysosomes. Other cell-surface molecules were expressed normally on immunocytes from PRAT4A−/− mice. There was impaired cytokine production to TLR ligands, except to the TLR3 ligand poly(I:C), and to whole bacteria. Activation of antigen-specific T helper type 1 responses were also defective. Moreover, PRAT4A−/− bone marrow chimeric mice were resistant to lipopolysaccharide-induced sepsis. These results suggest that PRAT4A regulates the subcellular distribution and response of multiple TLRs and is required for both innate and adaptive immune responses.

scholarly journals The Effect of Herpes Simplex Virus-Type-1 (HSV-1) Oncolytic Immunotherapy on the Tumor Microenvironment

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1200
Author(s):  
Ifeanyi Kingsley Uche ◽  
Konstantin G. Kousoulas ◽  
Paul J. F. Rider
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Checkpoint Inhibitors ◽  
Significant Proportion ◽  
Simplex Virus

The development of cancer causes disruption of anti-tumor immunity required for surveillance and elimination of tumor cells. Immunotherapeutic strategies aim for the restoration or establishment of these anti-tumor immune responses. Cancer immunotherapies include immune checkpoint inhibitors (ICIs), adoptive cellular therapy (ACT), cancer vaccines, and oncolytic virotherapy (OVT). The clinical success of some of these immunotherapeutic modalities, including herpes simplex virus type-1 derived OVT, resulted in Food and Drug Administration (FDA) approval for use in treatment of human cancers. However, a significant proportion of patients do not respond or benefit equally from these immunotherapies. The creation of an immunosuppressive tumor microenvironment (TME) represents an important barrier preventing success of many immunotherapeutic approaches. Mechanisms of immunosuppression in the TME are a major area of current research. In this review, we discuss how oncolytic HSV affects the tumor microenvironment to promote anti-tumor immune responses. Where possible we focus on oncolytic HSV strains for which clinical data is available, and discuss how these viruses alter the vasculature, extracellular matrix and immune responses in the tumor microenvironment.

Understanding the increased risk of infections in diabetes: innate and adaptive immune responses in type 1 diabetes

Metabolism ◽  
2021 ◽  
pp. 154795
Author(s):  
Anna W.M. Janssen ◽  
Rinke Stienstra ◽  
Martin Jaeger ◽  
Alain J. van Gool ◽  
Leo A.B. Joosten ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Increased Risk

A Near-Infrared Light-Excitable Immunomodulating Nano-photosensitizer for Effective Photoimmunotherapy

2021 ◽  
Author(s):  
Yadan Zheng ◽  
Zhanzhan Zhang ◽  
Qi Liu ◽  
Ying Wang ◽  
Jialei Hao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Near Infrared ◽  
Tumor Ablation ◽  
Infrared Light ◽  
Near Infrared Light ◽  
Therapeutic Efficiency ◽  
Immunosuppressive Tumor Microenvironment

Photodynamic therapy has great potential for tumor ablation and the activation of antitumor immune responses. However, its overall therapeutic efficiency is often limited by the immunosuppressive tumor microenvironment. We developed...

Polyinosinic acid: polycytidylic acid promotes T helper type 1-specific immune responses by stimulating macrophage production of interferon-α and interleukin-12

1995 ◽  
Vol 25 (9) ◽  
pp. 2656-2660 ◽  
Author(s):  
Roberto Manetti ◽  
Francesco Annunziato ◽  
Ljiljana Tomasevic ◽  
Valeria Giannò ◽  
Paola Parronchi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Interleukin 12 ◽  
Interferon Α ◽  
T Helper ◽  
Polycytidylic Acid ◽  
Polyinosinic Acid ◽  
Helper Type
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