CCR8 (C-C Motif Chemokine Receptor 8)

P3, N=400, Recruiting, LaNova Medicines Limited | Not yet recruiting --> Recruiting

A deeper understanding of Treg regulation is needed to unlock their therapeutic potential without compromising immune equilibrium.

This study provides a comprehensive single-cell resource for LS-associated CRC and highlights DMBT1 loss, epithelial remodelling, and immune dysregulation as potential therapeutic targets.

TL1A serves a dual role as a biomarker and therapeutic target in asthma, as it modulates macrophage-driven pathogenesis. TL1A inhibition disrupts CCL8/C-C motif chemokine receptor 8 signaling and pathogenic T-cell responses, providing a precision medicine strategy for asthma.

P1/2, N=52, Not yet recruiting, Nanjing Immunophage Biotech Co., Ltd

P1, N=99, Terminated, BeiGene | N=263 --> 99 | Trial completion date: Mar 2027 --> Jan 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2027 --> Jan 2026; This decision was conducted by the sponsor and not driven by safety concerns as no new safety signals have been observed in the CCR8 program.

Our findings establish that the CCR8/CCL1 axis drives the formation of an immunosuppressive niche in the liver by recruiting both Tregs and functionally suppressed CCR8+ T cells, thereby facilitating parasite immune evasion. This study not only elucidates a pivotal mechanism of immune escape in AE but also identifies CCR8 as a promising novel immunotherapeutic target for this neglected tropical disease.

Importantly, therapeutic neutralization of CCL1 using a monoclonal antibody significantly prolonged median survival in both immunocompetent GL261 murine GBM and BNI1-3 patient-derived xenograft (PDX) models, accompanied by reduced TAM infiltration and attenuated FAK/PI3K-AKT signaling. Our findings establish TAM-derived CCL1 as a pivotal regulator of GBM pathogenesis and demonstrate that targeting the CCL1-AMFR axis disrupts both tumor-intrinsic growth and immunosuppressive TME dynamics, representing a promising therapeutic strategy for this lethal malignancy.

Therapeutically, agents targeting chemokine pathways, most notably the CCR4 monoclonal antibody Mogamulizumab, have demonstrated clinical efficacy, while emerging inhibitors of CCR6, CCR5, and CXCR4 offer promising avenues for intervention. We further highlight how recent single-cell and other high-dimensional omics studies refine cell-type-specific chemokine sources and receptor expression, enabling more precise mapping of chemokine-driven intercellular communication programs in CTCL TME remodeling and better prioritization of therapeutic targets and biomarkers.

Additionally, efficacy of combination therapy was CD8 T cell dependent. These findings highlight the potential of combining RT with Treg-targeting therapies to enhance anti-tumor immunity.

P3, N=400, Not yet recruiting, LaNova Medicines Limited

In vivo efficacy studies were conducted using the EMT6 syngeneic breast tumor model, characterized by an immunosuppressive tumor microenvironment, assessing the antitumor effects of a CCR8-targeted small molecule (IPG7236) as monotherapy or in combination with anti-PD-L1 treatment...This study identifies Treg-enriched and immunosuppressive breast cancer subtype through integrative multi-omics analysis and demonstrates, through both in-silico and in-vivo approaches, the therapeutic potential of combining Treg-targeted and PD-L1 blockade therapies. These findings highlight Treg-mediated immunosuppression as a key determinant of therapeutic responsiveness, providing a biological rationale for patient stratification and guiding the development of personalized combination strategies for clinical translation.