CCR6 (C-C Motif Chemokine Receptor 6)

We further detail past and ongoing therapeutic efforts and trials addressing these axes in both PDAC and relevant non-PDAC settings via several small-molecule antagonists and monoclonal antibodies: BMS-813160, Maraviroc, Leronlimab, FLX475, PF-07054894, IDOR- 1117-2520, and CAP-100. Despite continuous advances in the field, the current body of evidence remains limited and presents significant research gaps in areas such as spatial profiling, stage-specific analyses, and general mechanistic validation in PDAC-specific settings. Addressing these shortcomings will be key to developing a more comprehensive knowledge of the field and improving future therapeutic strategies to overcome PDAC.

Targeting HSPB1 exerts dual anti-tumor effects: it directly suppresses neoplastic proliferation and simultaneously alleviates Treg-mediated immunosuppression within the tumor microenvironment.

Furthermore, CCR6 inhibition potentiated the efficacy of anti-PD1 immune checkpoint blockade. Taken together, our data demonstrate that tumor cell-derived CCL20 shapes an immunosuppressive microenvironment in pancreatic cancer by recruiting CCR6+ Tregs, suggesting that targeting the CCL20-CCR6 axis offers a promising therapeutic strategy, particularly when combined with immune checkpoint blockade.

In vitro and in vivo experiments validated the therapeutic potential of the CCR6-MM and R848 combination, demonstrating biocompatibility, macrophage polarization efficacy, and dual inhibitory effects on tumor growth and metastasis. Our findings highlight the potential of chemokine nanosponges as a novel therapeutic strategy for NSCLC metastasis.

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.

Finally, we highlight two regulatory modules-hypoxia-lactate/adenosine and lipid-ligand tuning of the RORγt ligand-binding domain-as plausible upstream levers that could remodel antigen presentation and type-3 outputs. Translational implications-including RORγt agonism, TME remodeling, and stage-aware biomarker hypotheses with minimally invasive profiling in malignant pleural effusion-are presented as testable hypotheses requiring validation in stage-resolved human NSCLC cohorts and mechanistic studies.

Hence, we designed a degradable embolic microsphere (RegFe@MS) capable of simultaneously loading hydrophobic regorafenib and magnetic iron oxide nanoparticles...This strategy can not only inhibit the post-embolization angiogenic response but also maximally suppress the proliferation and invasion of residual tumors. Furthermore, RegFe@MS has demonstrated remarkable therapeutic effects in the rabbit orthotopic liver cancer model.

In line with this, pathway enrichment analysis revealed immunosuppressive effects related to T cell regulation, similar to UV radiation-induced response. This study provides the first evidence of the efficacy of radon treatment, including the underlying mechanisms in a preclinical mouse model.

The main observations in the luminal A breast cancer group included a significant increase in neutrophils, plasmacytoid dendritic cells (pDCs), and CD4+ follicular T lymphocytes, as well as a reduced percentage of monocytes, conventional type 2 dendritic cells (cDC2), and CD4+CD196+ T cells. Despite being a preliminary study, these findings highlight distinct immune alterations in luminal A breast cancer and support the use of flow cytometry for identifying biomarkers, measurable biological indicators of disease presence, progression, or therapeutic response.

The observed pathways align with prior studies implicating IL-17 and a senescence-associated IL-6/CCR6 axis, extending these findings into a quantitative, time-resolved framework. This multimodal resource bridges molecular, morphological, and functional scales, providing a platform for mechanistic and therapeutic studies of RD.

Notably, CAR-E276 also exhibited potential for off-the-shelf and allogeneic applications. These findings are expected to offer valuable insights and drive the development of CAR-T therapies targeting solid tumors.