scholarly journals Immunobiology of cancer-associated fibroblasts in the context of radiotherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Turid Hellevik ◽  
Rodrigo Berzaghi ◽  
Kristin Lode ◽  
Ashraful Islam ◽  
Inigo Martinez-Zubiaurre
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Immune Cells ◽  
Growth Arrest ◽  
Present Knowledge ◽  
Immune Recognition ◽  
Cancer Associated Fibroblasts ◽  
Tumor Immune Evasion ◽  
Effects Of Radiation ◽  
Therapeutic Irradiation

AbstractRadiotherapy (RT) still represents a mainstay of treatment in clinical oncology. Traditionally, the effectiveness of radiotherapy has been attributed to the killing potential of ionizing radiation (IR) over malignant cells, however, it has become clear that therapeutic efficacy of RT also involves activation of innate and adaptive anti-tumor immune responses. Therapeutic irradiation of the tumor microenvironment (TME) provokes profound cellular and biological reconfigurations which ultimately may influence immune recognition. As one of the major constituents of the TME, cancer-associated fibroblasts (CAFs) play central roles in cancer development at all stages and are recognized contributors of tumor immune evasion. While some studies argue that RT affects CAFs negatively through growth arrest and impaired motility, others claim that exposure of fibroblasts to RT promotes their conversion into a more activated phenotype. Nevertheless, despite the well-described immunoregulatory functions assigned to CAFs, little is known about the interplay between CAFs and immune cells in the context of RT. In this review, we go over current literature on the effects of radiation on CAFs and the influence that CAFs have on radiotherapy outcomes, and we summarize present knowledge on the transformed cellular crosstalk between CAFs and immune cells after radiation.

scholarly journals Epigenetic dysregulation of immune-related pathways in cancer: bioinformatics tools and visualization

2021 ◽  
Author(s):  
Anders Berglund ◽  
Ryan M. Putney ◽  
Imene Hamaidi ◽  
Sungjune Kim
Keyword(s):  
Patient Outcome ◽  
Immune Responses ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Epigenetic Regulation ◽  
Current Evidence ◽  
Immune Recognition ◽  
Bioinformatics Tools ◽  
Visualization Techniques ◽  
Cancer Bioinformatics

AbstractCancer immune evasion is one of the hallmarks of carcinogenesis. Cancer cells employ multiple mechanisms to avoid immune recognition and suppress antitumor immune responses. Recently, accumulating evidence has indicated that immune-related pathways are epigenetically dysregulated in cancer. Most importantly, the epigenetic footprint of immune-related pathways is associated with the patient outcome, underscoring the crucial need to understand this process. In this review, we summarize the current evidence for epigenetic regulation of immune-related pathways in cancer and describe bioinformatics tools, informative visualization techniques, and resources to help decipher the cancer epigenome.

scholarly journals Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

2016 ◽  
Vol 90 (8) ◽  
pp. 3810-3818 ◽  
Author(s):  
Bjoern Meyer ◽  
Hinh Ly
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Multiorgan Failure ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Lassa Virus ◽  
Immune Recognition ◽  
African Countries ◽  
Host Immune Responses

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.

scholarly journals CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

2021 ◽  
Vol 11 ◽  
Author(s):  
Gurcan Gunaydin
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Poor Prognosis ◽  
Cancer Associated Fibroblasts ◽  
Mutual Relationship ◽  
Complex Interplay ◽  
Tumor Immune Evasion ◽  
Mechanisms Of Carcinogenesis

Cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs) are among the most important and abundant players of the tumor microenvironment. CAFs as well as TAMs are known to play pivotal supportive roles in tumor growth and progression. The number of CAF or TAM cells is mostly correlated with poor prognosis. Both CAFs and TAMs are in a reciprocal communication with the tumor cells in the tumor milieu. In addition to such interactions, CAFs and TAMs are also involved in a dynamic and reciprocal interrelationship with each other. Both CAFs and TAMs are capable of altering each other’s functions. Here, the current understanding of the distinct mechanisms about the complex interplay between CAFs and TAMs are summarized. In addition, the consequences of such a mutual relationship especially for tumor progression and tumor immune evasion are highlighted, focusing on the synergistic pleiotropic effects. CAFs and TAMs are crucial components of the tumor microenvironment; thus, they may prove to be potential therapeutic targets. A better understanding of the tri-directional interactions of CAFs, TAMs and cancer cells in terms of tumor progression will pave the way for the identification of novel theranostic cues in order to better target the crucial mechanisms of carcinogenesis.

scholarly journals The HHV-6A Proteins U20 and U21 Target NKG2D Ligands to Escape Immune Recognition

2021 ◽  
Vol 12 ◽  
Author(s):  
Abigael Eva Chaouat ◽  
Barbara Seliger ◽  
Ofer Mandelboim ◽  
Dominik Schmiedel
Keyword(s):  
Immune System ◽  
Immune Evasion ◽  
Immune Cells ◽  
Immune Escape ◽  
Human Herpesvirus ◽  
Immune Recognition ◽  
Nkg2d Ligand ◽  
Human Immune System ◽  
Nkg2d Ligands ◽  
Infected Cells

The coevolution of the human immune system and herpesviruses led to the emergence and diversification of both cellular danger molecules recognized by immune cells on the one hand and viral countermeasures that prevent the expression of these proteins on infected cells on the other. There are eight ligands for the activating receptor NKG2D in humans – MICA, MICB, ULBP1-6. Several of them are induced and surface-expressed on herpesvirus-infected cells to serve as danger signals to activate the immune system. Therefore, these ligands are frequently targeted for suppression by viral immune evasion mechanisms. Mechanisms to downregulate NKG2D ligands and thereby escape immune recognition have been identified in all other human herpesviruses (HHV), except for HHV-6A. In this study, we identify two HHV-6A encoded immunoevasins, U20 and U21, which suppress the expression of the NKG2D ligands ULBP1 and ULBP3, respectively, during infection. Additionally, MICB is targeted by a so far unexplored viral protein. Due to the diminished NKG2D ligand surface expression on infected cells, recognition of HHV-6A infected cells by innate immune cells is impaired. Importantly, our study indicates that immune escape mechanisms between the related herpesviruses HHV-6A and HHV-6B are evolutionary conserved as the same NKG2D ligands are targeted. Our data contribute an additional piece of evidence for the importance of the NKG2D receptor – NKG2D ligand axis during human herpesvirus infections and sheds light on immune evasion mechanisms of HHV-6A.

scholarly journals Cancer-Associated Fibroblasts: Accomplices in the Tumor Immune Evasion

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2969 ◽  
Author(s):  
Marc Hilmi ◽  
Rémy Nicolle ◽  
Corinne Bousquet ◽  
Cindy Neuzillet
Keyword(s):  
Tumor Microenvironment ◽  
Immune Evasion ◽  
Lymphoid Cells ◽  
Cancer Associated Fibroblasts ◽  
Tumor Immune Evasion ◽  
Promising Strategy ◽  
Extracellular Matrix Components ◽  
Potential Applications ◽  
Matrix Components

Cancer-associated fibroblasts (CAFs) are prominent cells within the tumor microenvironment, by communicating with other cells within the tumor and by secreting the extracellular matrix components. The discovery of the immunogenic role of CAFs has made their study particularly attractive due to the potential applications in the field of cancer immunotherapy. Indeed, CAFs are highly involved in tumor immune evasion by physically impeding the immune system and interacting with both myeloid and lymphoid cells. However, CAFs do not represent a single cell entity but are divided into several subtypes with different functions that may be antagonistic. Considering that CAFs are orchestrators of the tumor microenvironment and modulate immune cells, targeting their functions may be a promising strategy. In this review, we provide an overview of (i) the mechanisms involved in immune regulation by CAFs and (ii) the therapeutic applications of CAFs modulation to improve the antitumor immune response and the efficacy of immunotherapy.

scholarly journals Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yu-Pei Chen ◽  
Jia-Wei Lv ◽  
Yan-Ping Mao ◽  
Xiao-Min Li ◽  
Jun-Yan Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Immune Responses ◽  
Immune Evasion ◽  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Tumour Microenvironment ◽  
The Novel ◽  
Significant Enrichment

AbstractCurrently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.

scholarly journals The Roles of CD4+ T Cells in Tumor Immunity

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Yo-Ping Lai ◽  
Chung-Jiuan Jeng ◽  
Shu-Ching Chen
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Immune Evasion ◽  
Memory T Cells ◽  
Cytotoxic T Cells ◽  
Cell Manipulation ◽  
Tumor Immune Evasion ◽  
T Cell Help

Activation of CD8+ cytotoxic T cells has long been regarded as a major antitumor mechanism of the immune system. Emerging evidence suggests that CD4+ T cells are required for the generation and maintenance of effective CD8+ cytotoxic and memory T cells, a phenomenon known as CD4+ T-cell help. CD4+ T-cell help facilitates the optimal expansion, trafficking, and effector function of CD8+ T cells, thereby enhancing tumor destruction. In addition, a specialized subset of CD4+ T cells, CD4+CD25+ regulatory T cells (TRegs), effectively hampers anti-tumor immune responses, which has been proposed to be one of the major tumor immune evasion mechanisms. Here, we review recent advances in deciphering how anti-tumor immune responses are orchestrated by CD4+ T cells. We will also discuss the immunotherapeutic potential of CD4+ T-cell manipulation in anti-tumor immune response.

scholarly journals Malaria parasite evades mosquito immunity by glutaminyl cyclase mediated protein modification

2021 ◽  
Author(s):  
Surendra Kumar Kolli ◽  
Alvaro Molina-Cruz ◽  
Tamasa Araki ◽  
Fiona J.A. van Geurten ◽  
Jai Ramesar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Malaria Parasite ◽  
Protein Modification ◽  
Surface Protein ◽  
Surface Proteins ◽  
Immune Recognition ◽  
Post Translational Modification ◽  
Glutaminyl Cyclase ◽  
Major Mechanism

Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic acid (pGlu). Here, we report the biochemical and functional analysis of Plasmodium QC. We show that Plasmodium sporozoites of QC-null mutants are recognized by the mosquito immune system and melanized when they reach the hemocoel. Sporozoite numbers in salivary glands are also reduced in mosquitoes infected with QC-null or QC catalytically-dead mutants. This phenotype can be rescued by genetic complementation or by disrupting mosquito hemocytes or melanization immune responses. Mutation of a single QC-target glutamine of the major sporozoite surface protein (CSP) also results in immune recognition of sporozoites. These findings reveal QC-mediated post-translational modification of surface proteins as a major mechanism of mosquito immune evasion by Plasmodium sporozoites.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

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