Abstract
The immune system is an important defense mechanism against cancer and is often dysfunctional in patients with malignancies. The central regulator of the anti-cancer adaptive immune response is the T lymphocyte. T lymphocyte activation requires the completion of a carefully orchestrated series of specific steps that can be preempted or disrupted by any number of critical events. Particularly important is the provision of a costimulatory signal, the binding of accessory molecules on the antigen presenting cell to receptors on the T lymphocyte. Though costimulatory signals were traditionally envisioned as T lymphocyteactivating events, recent discoveries have highlighted their duality: they can be either stimulatory (costimulation) or inhibitory (coinhibition). In this article we review costimulation and coinhibition as potential targets for cancer therapy. We begin by presenting a general framework for thinking about the immune system in the context of cancer. Our discussion then bridges the various aspects of immune dysfunction seen in cancer with the presence of coinhibitory (ex: PD-1, PD-L1, CTLA-4, BTLA) and costimulatory (ex: CD28, ICOS, 4-1BB, CD40, OX40, CD27) signaling. Lastly, we develop a model of cancerrelated immune dysfunction that parallels the concept of immunoediting. Throughout the article we emphasize clinically relevant research often applicable-but not limited-to the example of renal cell carcinoma.
Keywords: Costimulation, coinhibition, tumor immunology, immunoediting, immunotherapy, T lymphocyte
Current Cancer Drug Targets
Title: Costimulation, Coinhibition and Cancer
Volume: 7 Issue: 1
Author(s): Brant A. Inman, Xavier Frigola, Haidong Dong and Eugene D. Kwon
Affiliation:
Keywords: Costimulation, coinhibition, tumor immunology, immunoediting, immunotherapy, T lymphocyte
Abstract: The immune system is an important defense mechanism against cancer and is often dysfunctional in patients with malignancies. The central regulator of the anti-cancer adaptive immune response is the T lymphocyte. T lymphocyte activation requires the completion of a carefully orchestrated series of specific steps that can be preempted or disrupted by any number of critical events. Particularly important is the provision of a costimulatory signal, the binding of accessory molecules on the antigen presenting cell to receptors on the T lymphocyte. Though costimulatory signals were traditionally envisioned as T lymphocyteactivating events, recent discoveries have highlighted their duality: they can be either stimulatory (costimulation) or inhibitory (coinhibition). In this article we review costimulation and coinhibition as potential targets for cancer therapy. We begin by presenting a general framework for thinking about the immune system in the context of cancer. Our discussion then bridges the various aspects of immune dysfunction seen in cancer with the presence of coinhibitory (ex: PD-1, PD-L1, CTLA-4, BTLA) and costimulatory (ex: CD28, ICOS, 4-1BB, CD40, OX40, CD27) signaling. Lastly, we develop a model of cancerrelated immune dysfunction that parallels the concept of immunoediting. Throughout the article we emphasize clinically relevant research often applicable-but not limited-to the example of renal cell carcinoma.
Export Options
About this article
Cite this article as:
Inman A. Brant, Frigola Xavier, Dong Haidong and Kwon D. Eugene, Costimulation, Coinhibition and Cancer, Current Cancer Drug Targets 2007; 7 (1) . https://dx.doi.org/10.2174/156800907780006878
DOI https://dx.doi.org/10.2174/156800907780006878 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Bugs and Drugs: Oncolytic Virotherapy in Combination with Chemotherapy
Current Pharmaceutical Biotechnology Editorial from Guest Editor (DNA Methylation: A Target for Current and Future Therapies?)
Epigenetic Diagnosis & Therapy (Discontinued) Recently Patented Applications of Homologous Cellular and Extracellular Agents as Therapeutics or Targets for the Prevention of Restenosis Post- Angioplasty
Recent Patents on Cardiovascular Drug Discovery Substance Abuse, HIV-1 and Hepatitis
Current HIV Research Nuclear Medicine: Proof of Principle for Targeted Drugs in Diagnosis and Therapy
Current Pharmaceutical Design Molecular Mechanisms of Anti-cancer Action of Garlic Compounds in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry The Linkage Between Inflammation and Immune Tolerance: Interfering with Inflammation in Cancer
Current Cancer Drug Targets Melatonin Regulates Angiogenic Factors under Hypoxia in Breast Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Painful Peripheral Neuropathies
Current Neuropharmacology Deregulated Expression of miR-224 and its Target Gene: CD59 Predicts Outcome of Diffuse Large B-cell Lymphoma Patients Treated with R-CHOP
Current Cancer Drug Targets HSP90 Inhibitors: Current Development and Potential in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Novel HSP90 Inhibitor NVP-AUY922 Enhances the Anti-tumor Effect of Temsirolimus Against Oral Squamous Cell Carcinoma
Current Cancer Drug Targets Alcohol and the Cardiovascular System: A Double-Edged Sword
Current Pharmaceutical Design Parathyroid Hypertension: A Rare, but Curable form of Secondary Hypertension
Current Hypertension Reviews The Flavin-Containing Monoooxygenases (FMOs): Genetic Variation and its Consequences for the Metabolism of Therapeutic Drugs
Current Pharmacogenomics Systemic Therapies for Pancreatic Cancer - The Role of Pharmacogenetics
Current Drug Targets Currently Approved Poly (Adenosine Diphosphate-Ribose) Inhibitors in Ovarian Cancer: Current Status and Future Directions
Clinical Cancer Drugs Anti-EGFR Binding Nanobody Delivery System to Improve the Diagnosis and Treatment of Solid Tumours
Recent Patents on Anti-Cancer Drug Discovery Discovery and Development of Topoisomerase Inhibitors as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Incretin Pharmacology: A Review of the Incretin Effect and Current Incretin-Based Therapies
Cardiovascular & Hematological Agents in Medicinal Chemistry