CCR3 (C-C Motif Chemokine Receptor 3)

Our findings unveil CCL11 as a master regulator of the pro-tumorigenic niche post-resection, driving recurrence through coordinated immune evasion and promoting tumor invasiveness. Targeting the CCL11-CCR5/CCR3 axis presents a promising strategy to improve HCC surgical outcomes.

Gracillin, a natural compound, was identified as a CCL24 inhibitor and synergized with 5-fluorouracil and programmed cell death 1 monoclonal antibody therapies in allograft-bearing mice. CCL24 facilitates recruitment of CCR3+ TAMs, enhancing the immunosuppressive TME in CRC. Targeting CCL24 with agents like gracillin represents a promising therapeutic strategy.

IP PTX promotes the recruitment and activation of eosinophils with potent antitumor activity in the peritoneal cavity. Early post-treatment abdominal eosinophilia is a robust prognostic biomarker and may represent a promising therapeutic target to enhance the efficacy of IP chemotherapy in patients with PM from GC.

CCL14 is a critical regulatory molecule within the LAM microenvironment and a promising biomarker for disease severity and progression.

In conclusion, CCL11 over-production drives HSC activation, creating an ECM-disorganized and immunosuppressive TME via the CCL11/CCR3 axis in LEN-treated HCC. Combination therapy with CCR3 inhibitor and LEN might represent a novel therapeutic strategy.

In this study, we identified a subtype of immunosuppressive (M2-like) programmed death ligand 1-positive (PD-L1+) tumor-associated macrophages (TAMs) critically fostering resistance to tamoxifen (TMX) and fulvestrant (FV) through maintaining cancer stem cell (CSC) activity in new mouse models. These TAMs are recruited by Delta-like ligand 1 (DLL1), a Notch signaling ligand expressed in luminal tumor cells, through the CCR3/CCL7 axis. Combination therapy with anti-DLL1 and anti-PD-L1 antibodies with TMX reduced tumor growth and associated CSCs and reprogrammed the immunosuppressive TME in both preclinical mouse models and patient-derived explants, thus laying the foundation for a future combined immune-endocrine therapy in these patients.

Notably, macrophages with similar iron- regulating features were found in human bone metastases across multiple cancer types, and elevated HBB expression in breast cancer correlates with increased risk of bone metastasis. These findings establish iron-recycling macrophages as essential regulators within the metastatic bone niche, revealing novel insights into the interplay between immune modulation, metal metabolism and tumor cell plasticity in driving metastatic progression and anemia.

Using a GC liver metastasis model in combination with PET-CT imaging, inhibition of the CCL11/CCR3 axis was shown to suppress CEH-driven tumor growth and metastatic potential. These findings identify LTBP1-enriched EVs from PDPN⁺LTBP1⁺ CAFs as a viable therapeutic target to impede GC liver metastasis.

The area under the curve (AUC) for CCL26 and CCR3 in predicting poor prognosis was 0.709 and 0.751, respectively, increasing to 0.798 when combined. Serum CCL26 and CCR3 levels decrease following azithromycin treatment and demonstrate significant associations with inflammatory markers and clinical outcomes, serving as reliable predictors for poor prognosis in MPP patients.

In addition, IL-1β was associated with rs689466, LY96 with rs2228014, rs5743336 genotypes (P < 0.05). As a conclusion, the CCR3 gene rs4987053, COX-2 gene rs689466, and NOD1 gene rs5743336 variations were determined to be closely associated with prostate cancer risk.

We identify macrophages with similar iron-transporting features in human bone metastases and show that elevated HBB expression correlates with increased risk of bone metastasis. These findings establish iron-transporting macrophages as an essential component of the metastatic bone niche, revealing a critical interplay between immune cells, metal metabolism, and tumor cell plasticity in driving metastasis and anemia.

Our data highlight several CRs as candidate prognostic markers and potential therapeutic targets in the context of POD24, warranting further investigation in larger, prospective cohorts. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.