Medical University of Vienna researchers have unveiled a groundbreaking combination immunotherapy approach that could transform the treatment landscape for melanoma and breast cancer patients. The innovative therapy, combining systemic interferon-I administration with topical imiquimod application, has demonstrated remarkable efficacy in targeting both primary tumors and distant metastases.
Dual-Action Therapeutic Mechanism
The research team, led by Maria Sibilia at the Center for Cancer Research, discovered that the combination therapy works through a sophisticated dual mechanism. Oral imiquimod stimulates plasmacytoid dendritic cells (pDCs) to produce interferon-I, which then sensitizes other dendritic cells and macrophages in the tumor microenvironment. This sensitization enhances the response to topical imiquimod treatment, ultimately leading to tumor cell death through the inhibition of blood vessel formation via IL12 signaling.
"Topical treatment of the primary tumor with imiquimod is essential for this combination therapy with systemic IFN-I to be effective at the treated site and also to clear distant metastases," explains Philipp Novoszel, one of the study's first authors.
Enhanced Metastasis Control and Immunological Response
A particularly promising aspect of the therapy is its ability to address one of cancer treatment's greatest challenges: controlling metastatic spread. The combination not only reduced the formation of new metastases but also increased melanoma sensitivity to checkpoint inhibitors, potentially preventing tumor recurrence.
"These findings illustrate that the combination of systemic treatment with imiquimod or IFN-I and topical therapy with imiquimod has the potential to expand treatment options for patients and improve therapy outcomes in locally accessible tumors such as melanoma or breast cancer," states Maria Sibilia.
Clinical Translation Potential
The research team is optimistic about the therapy's potential clinical applications. Martina Sanlorenzo, a dermato-oncologist at MedUni Vienna and co-first author, notes, "As systemic interferon is a well-known cancer therapy and dendritic cells are activated in a similar way to our preclinical models, we believe that the new combination therapy can show an effect in patients."
Future Therapeutic Implications
The study, published in Nature Cancer, represents a significant step forward in immunotherapy research. The team continues to focus on developing improved immunotherapeutic strategies, particularly for patients who currently show limited response to existing treatments.
"Our aim is to continue developing immunotherapeutic strategies in order to improve the long-term prospects for patients who are not yet responding well to these agents," emphasizes Sibilia, who also serves as Deputy Head of the Comprehensive Cancer Center at MedUni Vienna and University Hospital Vienna.
