CCR8 as a Therapeutic Novel Target: Omics-Integrated Comprehensive Analysis for Systematically Prioritizing Indications

Kim, Nari; Kim, Mi-Hyun; Pyo, Junhee; Lee, Soo-Min; Jang, Ji-Sung; Lee, Do-Wan; Kim, Kyung Won

doi:10.3390/biomedicines11112910

Cited by 3 publications

(2 citation statements)

References 49 publications

(66 reference statements)

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“…Interestingly, a correlation between cancer-associated fibroblasts (CAFs) and CCR8 has been found from the results of omics analysis. [22] CCR8 is suggested to be involved in the pathogenesis of various cancer types. CAFs are one of the tumor suppressor factors, the same as Treg, that are known to interfere with the function of tumor immune cells by promoting fibrosis and constructing an extracellular matrix in the TME.…”

Section: Discussionmentioning

confidence: 99%

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C<sub>8</sub>Mab-21: A Novel Anti-human CCR8 Monoclonal Antibody for Flow Cytometry

Tanaka,

Suzuki,

et al. 2024

Preprint

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C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (TH2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8+Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C8Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C8Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10-8 M and 2.0×10-8 M, respectively. C8Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

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Section: Discussionmentioning

confidence: 99%

“…[17,18] CCR8 is attractive as a target molecule for the next 2 cancer immunotherapy. [19] Anti-CCR8 drugs, including S-531011, [20] IPG7236, [21] and SRF114 [22] are undergoing clinical trials.…”

Section: Introductionmentioning

confidence: 99%

C<sub>8</sub>Mab-21: A Novel Anti-human CCR8 Monoclonal Antibody for Flow Cytometry

Tanaka,

Suzuki,

et al. 2024

Preprint

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Treg Cell Therapeutic Strategies for Breast Cancer: Holistic to Local Aspects

Zhang,

Felthaus,

Eigenberger

et al. 2024

Cells

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Regulatory T cells (Tregs) play a key role in maintaining immune homeostasis and preventing autoimmunity through their immunosuppressive function. There have been numerous reports confirming that high levels of Tregs in the tumor microenvironment (TME) are associated with a poor prognosis, highlighting their role in promoting an immunosuppressive environment. In breast cancer (BC), Tregs interact with cancer cells, ultimately leading to the suppression of immune surveillance and promoting tumor progression. This review discusses the dual role of Tregs in breast cancer, and explores the controversies and therapeutic potential associated with targeting these cells. Researchers are investigating various strategies to deplete or inhibit Tregs, such as immune checkpoint inhibitors, cytokine antagonists, and metabolic inhibition. However, the heterogeneity of Tregs and the variable precision of treatments pose significant challenges. Understanding the functional diversity of Tregs and the latest advances in targeted therapies is critical for the development of effective therapies. This review highlights the latest approaches to Tregs for BC treatment that both attenuate Treg-mediated immunosuppression in tumors and maintain immune tolerance, and advocates precise combination therapy strategies to optimize breast cancer outcomes.

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Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression

Wang,

Li,

Nakahata

et al. 2024

IJMS

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Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive T cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due to their immunosuppressive function, Tregs are thought to promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including tumor cells, infiltrating immune cells, and cancer-associated fibroblasts (CAFs). Within this environment, Tregs are recruited by chemokines and metabolic factors and impede effective anti-tumor responses. However, in some cases, their presence can also improve patient’s survival rates. Their functional consequences may vary across tumor types, locations, and stages. An in-depth understanding of the precise roles and mechanisms of actions of Treg is crucial for developing effective treatments, emphasizing the need for further investigation and validation. This review aims to provide a comprehensive overview of the complex and multifaceted roles of Tregs within the TME, elucidating cellular communications, signaling pathways, and their impacts on tumor progression and highlighting their potential anti-tumor mechanisms through interactions with functional molecules.

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CCR8 as a Therapeutic Novel Target: Omics-Integrated Comprehensive Analysis for Systematically Prioritizing Indications

Cited by 3 publications

References 49 publications

C<sub>8</sub>Mab-21: A Novel Anti-human CCR8 Monoclonal Antibody for Flow Cytometry

C<sub>8</sub>Mab-21: A Novel Anti-human CCR8 Monoclonal Antibody for Flow Cytometry

Treg Cell Therapeutic Strategies for Breast Cancer: Holistic to Local Aspects

Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression

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