Related Experiment Video
Updated: Feb 3, 2026
16:18
Microfluidic Device for Recreating a Tumor Microenvironment in Vitro
Published on: November 20, 2011
12.1K
CCR4 Antagonists Inhibit Treg Trafficking into the Tumor Microenvironment
John M Ketcham1, Lisa A Marshall1, Oezcan Talay1
1FLX Bio, Inc., 561 Eccles Avenue, South San Francisco, California 94080, United States.
ACS Medicinal Chemistry Letters
|October 23, 2018
Summary
Naturally occurring regulatory T cells (Treg) can hinder anti-tumor responses in cancer immunotherapy. New small molecule CCR4 antagonists effectively block Treg recruitment to the tumor microenvironment.
Area of Science:
- Immunology
- Oncology
Background:
- Regulatory T cells (Treg) expressing CD4, CD25, and FOXP3 suppress anti-tumor immunity.
- Treg cells are recruited to the tumor microenvironment (TME) via chemokines CCL17 and CCL22, mediated by CCR4.
- This Treg recruitment can diminish the effectiveness of immuno-oncology (IO) treatments.
Discussion:
- The study focuses on the role of Treg cells in the TME and their impact on IO therapy efficacy.
- It highlights the chemokine receptor CCR4 as a key mediator of Treg cell infiltration.
- The development of small molecule antagonists targeting CCR4 is presented as a novel therapeutic strategy.
Key Insights:
- Potent, orally bioavailable small molecule antagonists of CCR4 have been developed.
- These antagonists effectively block the recruitment of Treg cells into the TME.
- This blockade has the potential to enhance anti-tumor responses in patients undergoing IO therapy.
Outlook:
- Further preclinical and clinical studies are warranted to evaluate the efficacy of CCR4 antagonists in combination with IO agents.
- This approach may offer a new strategy to overcome resistance to cancer immunotherapy.
- Optimizing the delivery and dosage of these small molecules will be crucial for therapeutic success.
More Related Videos
08:32Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
10.4K
10:23Author Spotlight: Computing the Effects of a Local Radiofrequency Hyperthermia Intervention on Tumor Biomechanics
Published on: December 1, 2023
1.0K
Related Concept Videos
02:17The Tumor Microenvironment
7.8K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.8K
00:46Feedback Inhibition
57.1K
Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.1K
01:24Cholinergic Antagonists: Pharmacokinetics
962
Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations, while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and...
962
01:26Cholinergic Antagonists: Therapeutic Uses
1.5K
Antimuscarinic drugs have various therapeutic applications by inhibiting parasympathetic stimulation in different systems. Here are the key therapeutic uses of antimuscarinics:
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal...
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal...
1.5K
01:30Enzyme Inhibition
92.4K
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
92.4K
01:28Cholinergic Antagonists: Pharmacological Actions
1.7K
Antimuscarinic drugs block muscarinic receptors in multiple systems, including the gut, eye, smooth muscles, respiratory tract, cardiovascular, and central nervous systems. They produce similar effects with varying selectivity depending on the specific agent and tissue. Here are the key pharmacological actions of antimuscarinics:
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
1.7K