CCR8 (C-C Motif Chemokine Receptor 8)

Our findings suggest that CCR8⁺ Tregs suppress antitumor immunity in gastric cancer by affecting surrounding CD8⁺ T cells through spatial segregation. Targeting CCR8⁺ Tregs may offer a promising strategy to improve the efficacy of immunotherapy in gastric cancer.

111In-DOTA-Fab also exhibited pronounced kidney uptake which persisted even at 72 h. The kidney clearance and retention of 111In-DOTA-Fab might represent a problem during therapy employing 225Actimium or other long-lived therapeutic radionuclides by potentially causing a dose-limiting kidney toxicity. This imaging/biodistribution evaluation not only determined that full-size anti-CCR8 IgG is the optimal antibody format for pre-clinical development but also informed on the timing of immunotherapy administration in future radioimmunotherapy and immunotherapy combination studies.

Continued refinement through novel designs, such as conditionally activated or bispecific antibodies, will be essential to balance efficacy and safety. Together, these strategies hold potential to establish Treg depletion as a viable therapeutic modality in cancer.

These data demonstrate a synergistic effect of anti-aCCR8 RIT with immunotherapy through enhancement of adaptive and innate anti-tumor responses. Further investigation of anti-CCR8 RIT as a potential cancer-agnostic agent and its combinations with other immunotherapy agents such as anti-PD-1, LAG3 or TIGIT is warranted.

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.

It also explores the transition from a Th1 to a Th2 immune profile, linked to tumor progression. The dual role of chemokines in physiology and pathology is examined, with emphasis on their therapeutic potential in CTCL.

In vitro experiments using radiosensitive and radioresistant Tongue squamous cell carcinoma (TSCC) cell lines validated the association between chemokine gene expression and radiosensitivity. Our model provides a valuable tool for identifying HNSCC patients who may benefit from combined treatment strategies incorporating synergistic anti-tumor agents.

Moreover, FRP303 demonstrated strong synergistic effects when combined with a PD-1 antibody. In summary, FRP303 mediated anti-tumor activity through a dual mechanism involving the selective depletion of Ti-Tregs and the enhancement of CD8+ T cell function, offering a promising strategy for cancer immunotherapy.

Recent advances in antibody-based therapies and ligand-directed strategies, including cytotoxic CCL8 analogs, highlight new opportunities for translational application. Further research is needed to clarify its specific mechanisms and explore targeted interventions that modulate CCL8 signaling for clinical applications.

In vivo interventions targeting SLC3A2, SAT1, or CCL1 enhanced the antitumor effects of ICB therapy. Our findings provide insight into the mechanisms whereby metabolic reprogramming fosters an immunosuppressive TME, with implications for the treatment of HCC.

P1, N=263, Active, not recruiting, BeiGene | Recruiting --> Active, not recruiting