Overcoming Immunotherapy Resistance in Tumors: Targeting Treg Recruitment through CCR4 Regulation

3 June 2024
The abstract discusses the role of checkpoint inhibitors (CPIs) in cancer treatment and the challenges of resistance. It highlights the role of regulatory T cells (Treg) in resistance and their migration to tumors, which is mediated by the CC chemokine receptor 4 (CCR4). The study presents the development of a CCR4 antagonist, CCR4-351, to assess its impact on Treg migration and antitumor efficacy. Two mouse tumor models were used to evaluate the effects of the antagonist alone or in combination with CPIs.

The results indicate that the CCR4 inhibitor effectively reduces the migration of Treg into the tumor, leading to enhanced antitumor immune responses. In tumors with high baseline CCR4 ligand levels, CCR4 blockade decreased Treg numbers and improved immune activity. Interestingly, CPI treatment in tumors with low baseline CCR4 ligand levels led to an increase in these ligands and Treg numbers, which were reduced by CCR4 inhibition, thereby enhancing the CPIs' antitumor effects.

The conclusion emphasizes that CCR4-dependent Treg recruitment is a significant factor in immune resistance to cancer. The study supports the potential of combining CCR4 inhibitors with CPIs for cancer treatment, as it shows that blocking CCR4 can reduce Treg frequency and increase antitumor activity.

Lastly, the significance statement points out that CPIs can increase the expression of CCL17 and CCL22 in tumors, promoting Treg migration. The pharmacological targeting of the CCR4 receptor can effectively inhibit this migration and improve the antitumor efficacy of treatments, either as a standalone therapy in tumors with high CCR4 ligand expression or in combination with CPIs for tumors with low expression.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

图片包含 应用程序

描述已自动生成

Click on the image below to go directly to the Translational Medicine search interface.

图形用户界面, 文本, 应用程序, 电子邮件

描述已自动生成