Abstract
Human leukocyte antigen class I (HLA-I) presents antigenic peptides to cytotoxic CD8+ T cells (CTLs). This is a pivotal step in the generation of CTL responses. Both the quantity and quality of peptide-HLA-I (pHLA-I) complexes are crucial for CTL responses, but the level of HLA-I expression per se is also directly involved in dictating NK-cell responses. Antigen processing machinery (APM) proteins are involved in the maturation of HLA-I and in the selection of which peptides are – or are not – presented. Thus, these proteins are key players in shaping the immune response to cells in health and disease. In this review, we recap the most important features of APM components and their synergistic work to assure proper pHLA-I cell surface expression. We pay special attention to the HLA-I dedicated multifunctional protein, tapasin, and in relation to the different tapasin-dependency of HLA-I allomorphs we also discuss allomorph specific traits in maturation, structure and linkage to malignant diseases and brain tumors in particular. We next discuss the possibilities of restoring or manipulating the immune responses against brain tumors. In this context we discuss IFNγ therapy, cytostatics and irradiation. Finally, we integrate current views and knowledge to set the direction for future emphasis in the area of immunotherapy against brain tumors.
Keywords: Brain tumor, cytokine, HLA-I, MHC-I, tapasin.
Anti-Cancer Agents in Medicinal Chemistry
Title:HLA-I Antigen Presentation and Tapasin Influence Immune Responses Against Malignant Brain Tumors-Considerations for Successful Immunotherapy
Volume: 14 Issue: 8
Author(s): Anna Darabi, Camilla Thuring and Kajsa M. Paulsson
Affiliation:
Keywords: Brain tumor, cytokine, HLA-I, MHC-I, tapasin.
Abstract: Human leukocyte antigen class I (HLA-I) presents antigenic peptides to cytotoxic CD8+ T cells (CTLs). This is a pivotal step in the generation of CTL responses. Both the quantity and quality of peptide-HLA-I (pHLA-I) complexes are crucial for CTL responses, but the level of HLA-I expression per se is also directly involved in dictating NK-cell responses. Antigen processing machinery (APM) proteins are involved in the maturation of HLA-I and in the selection of which peptides are – or are not – presented. Thus, these proteins are key players in shaping the immune response to cells in health and disease. In this review, we recap the most important features of APM components and their synergistic work to assure proper pHLA-I cell surface expression. We pay special attention to the HLA-I dedicated multifunctional protein, tapasin, and in relation to the different tapasin-dependency of HLA-I allomorphs we also discuss allomorph specific traits in maturation, structure and linkage to malignant diseases and brain tumors in particular. We next discuss the possibilities of restoring or manipulating the immune responses against brain tumors. In this context we discuss IFNγ therapy, cytostatics and irradiation. Finally, we integrate current views and knowledge to set the direction for future emphasis in the area of immunotherapy against brain tumors.
Export Options
About this article
Cite this article as:
Darabi Anna, Thuring Camilla and Paulsson M. Kajsa, HLA-I Antigen Presentation and Tapasin Influence Immune Responses Against Malignant Brain Tumors-Considerations for Successful Immunotherapy, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (8) . https://dx.doi.org/10.2174/1871520614666140825110001
DOI https://dx.doi.org/10.2174/1871520614666140825110001 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Discovery of Lead compounds targeting transcriptional regulation
Transcriptional regulation plays key physiological functions in body growth and development. Transcriptional dysregulation is one of important biomarkers of tumor genesis and progression, which is involved in regulating tumor cell processes such as cell proliferation, differentiation, and apoptosis. Additionally, it plays a pivotal role in angiogenesis and promotes tumor metastasis ...read more
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Innovative targets in medicinal chemistry
Medicinal chemistry continuously evolves in response to emerging healthcare needs and advancements in scientific understanding. This special issue explores the current landscape of innovative targets in medicinal chemistry, highlighting the quest for novel therapeutic avenues. From traditional drug targets such as enzymes and receptors to emerging targets like protein-protein interactions ...read more
Metalloenzymes and Cancer: Μetalloenzyme Ιnhibitors and Artificial Metalloenzymes as anti-cancer agents
Metalloenzymes are enzymes containing metal ions, which are directly bound to the enzyme and play a role in promoting catalysis. About one-third of all enzymes known so far are metalloenzymes [1]. Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
A Novel Recombinant Modified Vaccinia Ankara Virus expressing
Interleukin-13 Receptor α2 Antigen for Potential Cancer
Immunotherapy
Current Molecular Medicine The Novel Functions of cGMP-Specific Phosphodiesterase 5 and its Inhibitors in Carcinoma Cells and Pulmonary/Cardiovascular Vessels
Current Topics in Medicinal Chemistry A Review of Select Recent Patents on Novel Nanocarriers
Recent Patents on Drug Delivery & Formulation The Expression, Function and Targeting of Haem Oxygenase-1 in Cancer
Current Cancer Drug Targets The Urokinase-type Plasminogen Activator and the Generation of Inhibitors of Urokinase Activity and Signaling
Current Pharmaceutical Design Functional Activity and Connectivity Differences of Five Resting-State Networks in Patients with Alzheimer’s Disease or Mild Cognitive Impairment
Current Alzheimer Research Amplicons as Vaccine Vectors
Current Gene Therapy Prognostic and Predictive Biomarkers in Cancer
Current Cancer Drug Targets The Urokinase Receptor Interactome
Current Pharmaceutical Design Himalayan Plants as a Source of Anti-Cancer Agents: A Review
The Natural Products Journal Can γH2AX be Used to Personalise Cancer Treatment?
Current Molecular Medicine Oncolytic Viruses for Induction of Anti-Tumor Immunity
Current Pharmaceutical Biotechnology ZIP4 is a Novel Diagnostic and Prognostic Marker in Human Pancreatic Cancer: A Systemic Comparison Between EUS-FNA and Surgical Specimens
Current Molecular Medicine Meet Our Editorial Board Member
Current Cancer Therapy Reviews Antidepressants and Neuroinflammation: Can Antidepressants Calm Glial Rage Down?
Mini-Reviews in Medicinal Chemistry Multimodality Imaging of CXCR4 in Cancer: Current Status towards Clinical Translation
Current Molecular Medicine <i>In Vitro</i> Effects of Propofol on Cytotoxic, Apoptotic and PI3K-Akt Signaling Pathway Genes on Brain Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Inhibitory Effect of Ebselen on Cerebral Acetylcholinesterase Activity In Vitro: Kinetics and Reversibility of Inhibition
Current Pharmaceutical Design Fibroblast Growth Factor Receptor Signaling in Cancer Biology and Treatment
Current Signal Transduction Therapy Near-infrared Light Activatable Multimodal Gold Nanostructures Platform: An Emerging Paradigm for Cancer Therapy
Current Cancer Drug Targets