Researchers at Moffitt Cancer Center in Florida have identified a new strategy to enhance the therapeutic efficacy of immune checkpoint inhibitors by targeting additional immunosuppressive compartments in the tumour microenvironment, such as the Macrophage Receptor with Collagenous Structure (MARCO). Published in the Journal for ImmunoTherapy of Cancer, the study shows that blocking MARCO in conjunction with administering anti-CTLA4 therapy can substantially improve tumour regression in patients with melanoma.
The study found that inhibiting MARCO alters the behaviour of specific immune cells within the tumour, leading to increased immune cell infiltration and heightened efficacy of anti-CTLA4 therapy. This innovative approach holds promise for overcoming resistance to current treatments, particularly in ‘cold’ tumours that are characterized by low immune cell presence.
“Our findings provide strong evidence that targeting MARCO can enhance the effectiveness of existing immunotherapies without requiring macrophage depletion,” James Mulé, PhD, associate center director for Translational Science at Moffitt and lead author of the study, said in a press release. "This discovery paves the way for new combination treatment strategies that could improve outcomes for patients with melanoma and potentially other cancers.”
The research highlights that combining an anti-MARCO monoclonal antibody with anti-CTLA4 therapy can significantly boost immune cell infiltration. That includes conventional dendritic cells, which are crucial for initiating a robust anti-tumour immune response. Notably, this synergistic effect was not observed when MARCO was targeted alongside anti-PD1 therapy, underscoring the importance of this approach in enhancing anti-CTLA4 treatment.
According to Dr. Mulé, these results open new avenues for clinical research and potentially offer solutions for patients who do not respond to current immunotherapy options. The study also suggests that incorporating MARCO-targeting strategies into neoadjuvant or adjuvant settings may help reduce cancer recurrence risks by enhancing immune priming within the tumour microenvironment.
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