Abstract
Human leukocyte antigen class I (HLA-I) molecules present antigenic peptides to cytotoxic CD8+ T cells. Downregulation of peptide:HLA-I complexes is common in tumors and results in tumor immune escape variants. Also molecules involved in the maturation of HLA-I have been demonstrated to be dysregulated in malignant neoplasms. We here set out to investigate the antigen presentation capabilities of a set of 12 glioblastoma multiforme (GBM) tumors based on the expression of HLA-I. Moreover, we analyzed the expression of tapasin, a protein dedicated and essential to HLA-I maturation, as well as the infiltration of CD8+ cells using immunohistochemistry on paraffin-embedded sections. Comparison of different GBMs showed a variation in expression of both HLA-I heavy chain (HC) and tapasin. Interestingly, the expression of tapasin and HLA-I HC correlated significantly (p=0.0002) suggesting tapasin to be a key factor for efficient HLA-I antigen presentation in GBMs. Although no statistically significant correlation between CD8+ cells and survival was found, probably due to a very low number of infiltrating CD8+ cells at the time of surgical resection, both tapasin and HLA-I HC levels significantly correlated with survival. We suggest that analysis of expression of tapasin and/or HLA-I may be of value as prognostic tool for GBM patients, especially when considering immunotherapy.
Keywords: Brain tumor, CD8, glioblastoma multiforme, HLA-I, MHC-I, tapasin.
Anti-Cancer Agents in Medicinal Chemistry
Title:Tapasin and Human Leukocyte Antigen Class I Dysregulation Correlates with Survival in Glioblastoma Multiforme
Volume: 14 Issue: 8
Author(s): Camilla Thuring, Linda Geironson and Kajsa Paulsson
Affiliation:
Keywords: Brain tumor, CD8, glioblastoma multiforme, HLA-I, MHC-I, tapasin.
Abstract: Human leukocyte antigen class I (HLA-I) molecules present antigenic peptides to cytotoxic CD8+ T cells. Downregulation of peptide:HLA-I complexes is common in tumors and results in tumor immune escape variants. Also molecules involved in the maturation of HLA-I have been demonstrated to be dysregulated in malignant neoplasms. We here set out to investigate the antigen presentation capabilities of a set of 12 glioblastoma multiforme (GBM) tumors based on the expression of HLA-I. Moreover, we analyzed the expression of tapasin, a protein dedicated and essential to HLA-I maturation, as well as the infiltration of CD8+ cells using immunohistochemistry on paraffin-embedded sections. Comparison of different GBMs showed a variation in expression of both HLA-I heavy chain (HC) and tapasin. Interestingly, the expression of tapasin and HLA-I HC correlated significantly (p=0.0002) suggesting tapasin to be a key factor for efficient HLA-I antigen presentation in GBMs. Although no statistically significant correlation between CD8+ cells and survival was found, probably due to a very low number of infiltrating CD8+ cells at the time of surgical resection, both tapasin and HLA-I HC levels significantly correlated with survival. We suggest that analysis of expression of tapasin and/or HLA-I may be of value as prognostic tool for GBM patients, especially when considering immunotherapy.
Export Options
About this article
Cite this article as:
Thuring Camilla, Geironson Linda and Paulsson Kajsa, Tapasin and Human Leukocyte Antigen Class I Dysregulation Correlates with Survival in Glioblastoma Multiforme, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (8) . https://dx.doi.org/10.2174/1871520614666140825110402
DOI https://dx.doi.org/10.2174/1871520614666140825110402 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
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
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- 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
-
Targeting Human Telomerase by Antisense Oligonucleotides and Ribozymes: An Update
Medicinal Chemistry Reviews - Online (Discontinued) The Chemopreventive and Chemotherapeutic Potentials of Tea Polyphenols
Current Pharmaceutical Biotechnology Pleiotropic Effects of Cathepsin D
Endocrine, Metabolic & Immune Disorders - Drug Targets Histone Deacetylase Inhibitors in Cancer Therapy: New Compounds and Clinical Update of Benzamide-Type Agents
Current Topics in Medicinal Chemistry The Role of Epigenetics in Drug Resistance in Cancer
Epigenetic Diagnosis & Therapy (Discontinued) Regulation of Mesenchymal Phenotype by MicroRNAs in Cancer
Current Cancer Drug Targets All for Statins and Statins for All; An Update
Current Pharmaceutical Design Phytocompounds from the Medicinal and Dietary Plants: Multi-target Agents for Cervical Cancer Prevention and Therapy
Current Medicinal Chemistry Relationship Between Body Mass Index and Reproduction
Current Women`s Health Reviews Toward The Rational Design of Cell Fate Modifiers Notch Signaling as a Target for Novel Biopharmaceuticals
Current Pharmaceutical Biotechnology Trabectedin (Yondelis®) as a Therapeutic Option in Gynecological Cancers: A Focus on its Mechanisms of Action, Clinical Activity and Genomic Predictors of Drug Response
Current Drug Targets MicroRNAs Regulate the Epithelial to Mesenchymal Transition (EMT) in Cancer Progression
MicroRNA New Development and Application of Ultrasound Targeted Microbubble Destruction in Gene Therapy and Drug Delivery
Current Gene Therapy Texture Analysis in the Evaluation of COVID-19 Pneumonia in Chest X-Ray Images: A Proof of Concept Study
Current Medical Imaging Endothelial Progenitor Cells: A Vascular Perspective for Inflammatory Rheumatic Disorders
Current Rheumatology Reviews Angiomodulatory and Neurological Effects of Ginsenosides
Current Medicinal Chemistry An Overview of Bioactive Peptides for in vivo Imaging and Therapy in Human Diseases
Mini-Reviews in Medicinal Chemistry IDO+ DCs and Signalling Pathways
Current Cancer Drug Targets Some Developments Regarding Functional Food Products (Functional Foods)
Current Nutrition & Food Science Using Pharmacologic Data to Plan Clinical Treatments for Patients with Peritoneal Surface Malignancy
Current Drug Discovery Technologies