scholarly journals The MYC oncogene is a global regulator of the immune response

Blood ◽  
2018 ◽  
Vol 131 (18) ◽  
pp. 2007-2015 ◽  
Author(s):  
Stephanie C. Casey ◽  
Virginie Baylot ◽  
Dean W. Felsher
Keyword(s):  
Immune Response ◽  
Cellular Growth ◽  
Therapeutic Interventions ◽  
Immune Checkpoints ◽  
Immune Effector ◽  
Effector Cells ◽  
Myc Oncogene ◽  
Induced Tumors ◽  
Programmed Death ◽  
Immune Detection

Abstract The MYC proto-oncogene is a gene product that coordinates the transcriptional regulation of a multitude of genes that are essential to cellular programs required for normal as well as neoplastic cellular growth and proliferation, including cell cycle, self-renewal, survival, cell growth, metabolism, protein and ribosomal biogenesis, and differentiation. Here, we propose that MYC regulates these programs in a manner that is coordinated with a global influence on the host immune response. MYC had been presumed to contribute to tumorigenesis through tumor cell–intrinsic influences. More recently, MYC expression in tumor cells has been shown to regulate the tumor microenvironment through effects on both innate and adaptive immune effector cells and immune regulatory cytokines. Then, MYC was shown to regulate the expression of the immune checkpoint gene products CD47 and programmed death-ligand 1. Similarly, other oncogenes, which are known to modulate MYC, have been shown to regulate immune checkpoints. Hence, MYC may generally prevent highly proliferative cells from eliciting an immune response. MYC-driven neoplastic cells have coopted this mechanism to bypass immune detection. Thus, MYC inactivation can restore the immune response against a tumor. MYC-induced tumors may be particularly sensitive to immuno-oncology therapeutic interventions.

Immune Self-tuning in Renal Cell Carcinoma

2010 ◽  
Vol 06 (01) ◽  
pp. 70
Author(s):  
Antonia Busse ◽  
Ulrich Keilholz ◽  
◽  
Keyword(s):  
Renal Cell Carcinoma ◽  
Immune Response ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Disease Stabilisation ◽  
Tumour Regression ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells ◽  
Inhibitory Molecules

Although renal cell carcinoma (RCC) is an immunogenic tumour, and although there is evidence that in a small proportion of cases antitumour immune responses may mediate tumour regression or at least disease stabilisation, patients with progressive disease have no effective antitumour immune response. Besides preventing recognition of the tumour by immune effector cells, RCC escapes the immune system by induction of tolerance through manipulating the function and proliferation of immune effector cells. This tuning of the immune response can occur by active suppression of immune effector cells through inhibitory molecules expressed on the tumour surface and through various tumour-secreted soluble factors, or it can be mediated indirectly by induction of immunosuppressive cells. This review provides an overview of the most common mechanisms that mediate immune tolerance in RCC and discusses the therapeutic perspectives of immunoregulatory strategies in the era of targeted therapies.

Cellular side of acquired immunity (T cells)

2013 ◽  
Author(s):  
Assia Eljaafari ◽  
Pierre Miossec
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Disease Process ◽  
T Cell Response ◽  
Th2 Cells ◽  
Cell Mediated Immunity ◽  
Immune Effector ◽  
Effector Cells ◽  
Th22 Cells

The adaptive T-cell response represents the most sophisticated component of the immune response. Foreign invaders are recognized first by cells of the innate immune system. This leads to a rapid and non-specific inflammatory response, followed by induction of the adaptive and specific immune response. Different adaptive responses can be promoted, depending on the predominant effector cells that are involved, which themselves depend on the microbial/antigen stimuli. As examples, Th1 cells contribute to cell-mediated immunity against intracellular pathogens, Th2 cells protect against parasites, and Th17 cells act against extracellular bacteria and fungi that are not cleared by Th1 and Th2 cells. Among the new subsets, Th22 cells protect against disruption of epithelial layers secondary to invading pathogens. Finally these effector subsets are regulated by regulatory T cells. These T helper subsets counteract each other to maintain the homeostasis of the immune system, but this balance can be easily disrupted, leading to chronic inflammation or autoimmune diseases. The challenge is to detect early changes in this balance, prior to its clinical expression. New molecular tools such as microarrays could be used to determine the predominant profile of the immune effector cells involved in a disease process. Such understanding should provide better therapeutic tools to counteract deregulated effector cells.

scholarly journals Listeriolysin O is a target of the immune response to Listeria monocytogenes.

1992 ◽  
Vol 175 (6) ◽  
pp. 1467-1471 ◽  
Author(s):  
H G Bouwer ◽  
C S Nelson ◽  
B L Gibbins ◽  
D A Portnoy ◽  
D J Hinrichs
Keyword(s):  
Immune Response ◽  
Listeria Monocytogenes ◽  
Gene Product ◽  
Cell Subset ◽  
Target Antigen ◽  
Target Cells ◽  
Listeriolysin O ◽  
Immune Effector ◽  
Effector Cells ◽  
Cytotoxic Cells

The immunologic mechanism of protective immunity to the intracellular parasite Listeria monocytogenes (Lm) is not well understood, however, antilisterial immunity can be adoptively transferred with T lymphocytes from Lm-immune donors. The Lm-immune cells are believed to produce macrophage-activating lymphokines, which leads to the eventual macrophage-dependent eradication of the bacterium. Increasing evidence suggests that immunity to Lm resides exclusively within the CD8+ T cell subset. It is possible that the Lm-immune CD8+ T cells function to release sequestered Lm from nonprofessional phagocytes to awaiting activated macrophage populations. This study was conducted to determine if listeriolysin O (LLO), which is an essential determinant of Lm pathogenicity, is also a target of the antilisterial immune response. We have found that target cells infected with a LLO+ Lm strain are lysed by Lm-immune cytotoxic cells, whereas target cells infected with a LLO- Lm mutant, or pulsed with a heat-killed Lm preparation, are not lysed by the Lm-immune effector cells. We have used a Bacillus subtilis (Bs) construct that expresses the LLO gene product and found that target cells infected with the LLO+ Bs construct are lysed by antilisterial cytotoxic cells. The antilisterial cytotoxic response is targeted against LLO, in that we have also used a Bs construct that expresses the perfringolysin (PLO) gene product and found that target cells infected with the PLO+ Bs are not lysed by antilisterial cytotoxic effector cells. These data strongly suggest that LLO is a target antigen of antilisterial immunity and may represent the dominant target during the expression of the immune response to Lm.

scholarly journals Harnessing NK Cell Checkpoint-Modulating Immunotherapies

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1807 ◽  
Author(s):  
Sachin Kumar Singh Chauhan ◽  
Ulrike Koehl ◽  
Stephan Kloess
Keyword(s):  
Immune Response ◽  
Immune Checkpoint ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Therapeutic Interventions ◽  
Immune Checkpoints ◽  
Effector Functions ◽  
Self Tolerance ◽  
Underlying Mechanisms

During the host immune response, the precise balance of the immune system, regulated by immune checkpoint, is required to avoid infection and cancer. These immune checkpoints are the mainstream regulator of the immune response and are crucial for self-tolerance. During the last decade, various new immune checkpoint molecules have been studied, providing an attractive path to evaluate their potential role as targets for effective therapeutic interventions. Checkpoint inhibitors have mainly been explored in T cells until now, but natural killer (NK) cells are a newly emerging target for the determination of checkpoint molecules. Simultaneously, an increasing number of therapeutic dimensions have been explored, including modulatory and inhibitory checkpoint molecules, either causing dysfunction or promoting effector functions. Furthermore, the combination of the immune checkpoint with other NK cell-based therapeutic strategies could also strengthen its efficacy as an antitumor therapy. In this review, we have undertaken a comprehensive review of the literature to date regarding underlying mechanisms of modulatory and inhibitory checkpoint molecules.

scholarly journals Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes

2021 ◽  
Author(s):  
Claudia Cocco ◽  
Fabio Morandi ◽  
Irma Airoldi
Keyword(s):  
Solid Tumors ◽  
T Cell Activation ◽  
Cell Activation ◽  
Vascular Endothelial Cells ◽  
Suppressor Cells ◽  
Immune Checkpoints ◽  
Cell Populations ◽  
Immune Effector ◽  
Effector Cells ◽  
Pediatric Solid Tumors

Tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulation of cellular functions. Many stimuli, on one hand, induce tumor growth and spread of metastatic cells and, on the other hand, contribute to the establishment of an immunosuppressive environment. The latter feature is achieved by soothing immune effector cells, mainly cytotoxic T lymphocytes, B and NK cells, and/or through expansion of regulatory cell populations, including regulatory T and B cells, tumor-associated macrophages and myeloid-derived suppressor cells. In this context, immune checkpoints (IC) are key players in the control of T cell activation and anti-cancer activities, leading to the inhibition of tumor cell lysis and of pro-inflammatory cytokine production. Thus, these pathways represent promising targets for the development of effective and innovative therapies both in adults and childhood. Here we address the role of different cell populations homing the TME and of well-known and recently characterized IC in the context of pediatric solid tumors. We also discuss preclinical and clinical data available using IC inhibitors alone, in combination each other or administered with standard therapies.

scholarly journals Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hong-Bo Li ◽  
Zi-Han Yang ◽  
Qing-Qu Guo
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Immune Effector ◽  
Effector Cells ◽  
Pathological Subtype

AbstractPancreatic cancer is an extremely malignant tumor with the lowest 5-year survival rate among all tumors. Pancreatic ductal adenocarcinoma (PDAC), as the most common pathological subtype of pancreatic cancer, usually has poor therapeutic results. Immune checkpoint inhibitors (ICIs) can relieve failure of the tumor-killing effect of immune effector cells caused by immune checkpoints. Therefore, they have been used as a novel treatment for many solid tumors. However, PDAC is not sensitive to monotherapy with ICIs, which might be related to the inhibitory immune microenvironment of pancreatic cancer. Therefore, the way to improve the microenvironment has raised a heated discussion in recent years. Here, we elaborate on the relationship between different immune cellular components in this environment, list some current preclinical or clinical attempts to enhance the efficacy of ICIs by targeting the inhibitory tumor microenvironment of PDAC or in combination with other therapies. Such information offers a better understanding of the sophisticated tumor-microenvironment interactions, also providing insights on therapeutic guidance of PDAC targeting.

scholarly journals Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II—The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer

2017 ◽  
Vol 142 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Esmeralda Celia Marginean ◽  
Barbara Melosky
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Microsatellite Instability ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Immune Checkpoints ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

Context.— The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti–programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability–high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability–high CRC. Objectives.— To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. Data Sources.— A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. Conclusions.— Exciting success with anti–PD-1/PD-L1 and anticytotoxic T-lymphocyte–associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability–high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti–PD-1 or anti–PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability–high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.

A role for altered phagosome maturation in the long-term persistence ofHelicobacter pyloriinfection

2012 ◽  
Vol 303 (2) ◽  
pp. G169-G179 ◽  
Author(s):  
Glenn N. Borlace ◽  
Stacey J. Keep ◽  
Mark J. R. Prodoehl ◽  
Hilary F. Jones ◽  
Ross N. Butler ◽  
...  
Keyword(s):  
Immune Response ◽  
Host Immune Response ◽  
Human Gastric Mucosa ◽  
Phagosome Maturation ◽  
Duodenal Ulcers ◽  
Immune Effector ◽  
Effector Cells ◽  
Gastric Or Duodenal Ulcers ◽  
H Pylori

The vigorous host immune response that is mounted against Helicobacter pylori is unable to eliminate this pathogenic bacterium from its niche in the human gastric mucosa. This results in chronic inflammation, which can develop into gastric or duodenal ulcers in 10% of infected individuals and gastric cancer in 1% of infections. The determinants for these more severe pathologies include host (e.g., high IL-1β expression polymorphisms), bacterial [e.g., cytotoxicity-associated gene ( cag) pathogenicity island], and environmental (e.g., dietary nitrites) factors. However, it is the failure of host immune effector cells to eliminate H. pylori that underlies its persistence and the subsequent H. pylori-associated disease. Here we discuss the mechanisms used by H. pylori to survive the host immune response and, in particular, the role played by altered phagosome maturation.

scholarly journals CURRENT UNDERSTANDING OF ANTITUMOR IMMUNITY

2015 ◽  
Vol 14 (3) ◽  
pp. 19-28 ◽  
Author(s):  
I. Zh. Shubina ◽  
A. V. Sergeev ◽  
L. T. Mamedova ◽  
N. Yu. Sokolov ◽  
M. V. Kiselevsky
Keyword(s):  
Immune Response ◽  
Antitumor Immunity ◽  
Nk Cell ◽  
Experimental Studies ◽  
Immune Defense ◽  
Immune Effector ◽  
Effector Cells ◽  
Adaptive Immune ◽  
Immune Effector Cells

The review presents analysis of the papers that discuss mechanisms of antitumor immunity. The role of innate and adaptive immune reactions as well as local and systemic is considered in terms of immune defense in clinical and experimental studies. The article discusses characteristics and role tumor-associated antigens for clinical practice. Various types of immune effector cells, including T-cells, NK-cell, DC, tumor associated macrophages, etc., and cytokines, are discussed regarding their contribution into antitumor immune response. The authors also refer to the hypothesis of “immunoediting” and its part in antitumor immunity.

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