A team of researchers from the Medical University of Vienna, led by Maria Sibilia, has explored a novel combination therapy for cancer treatment. This approach involves administering the tissue hormone interferon-I throughout the body along with a localized application of Imiquimod. The results have been promising, particularly for tumors that can be accessed topically, such as melanoma and breast cancer. The therapy has resulted in tumor cell death at the treatment sites while simultaneously boosting the body’s adaptive immune response to combat distant metastases. Findings published in the prestigious journal Nature Cancer suggest improvements in treating surface-level tumors like melanoma and breast cancer.
Immunotherapy has seen remarkable success in tackling various types of cancer in recent years. However, some patients still do not respond well to these therapies. In a preclinical study, Maria Sibilia, who heads the Center for Cancer Research at the Medical University of Vienna, examined the effects of a combination immunotherapy that includes the systemic use of the tissue hormone interferon (IFN)-I along with local treatment using Imiquimod. Imiquimod, an active agent known for activating innate receptors TLR7/8, is often used to treat basal cell carcinomas. The researchers conducted their experiments on different preclinical mouse models of melanoma and breast cancer, both of which are amenable to local treatment and can frequently develop distant metastases.
Effective for localized tumors and distant spread
This type of immunotherapy harnesses the body’s immune system to target and destroy cancer cells. Key to this process are plasmacytoid dendritic cells (pDCs), which are activated by Imiquimod through TLR7/8. The study found that Imiquimod prompts pDCs to produce interferon-I, which in turn sensitizes other dendritic cells and macrophages in the tumor microenvironment. This leads to angiogenesis inhibition through the cytokine IL12, resulting in the death of tumor cells. Remarkably, the combination immunotherapy not only impacted the treated tumors but also affected distant metastases, thereby reducing the formation of new metastatic sites and minimizing the chances of tumor recurrence. Additionally, it improved the response of melanoma tumors to checkpoint inhibitors.
“These findings demonstrate that combining systemic treatment with Imiquimod or interferon-I and topical therapy using Imiquimod can broaden treatment choices for patients, enhancing outcomes for localized tumors like melanoma or breast cancer,” highlights Maria Sibilia. “For this combination therapy to be effective at the treatment site and to eliminate distant metastases, applying Imiquimod to the primary tumor is crucial,” adds Philipp Novoszel, a co-author from MedUni Vienna.
The results indicate that this therapeutic approach may enhance treatment efficacy for superficial and locally manageable tumors such as melanoma and breast cancer—achieving this through localized tumor cell death as well as fostering a T cell-driven anti-tumor immune response in distant metastases, further amplified by checkpoint inhibitors.
“Our goal is to advance immunotherapeutic strategies to improve long-term outcomes for patients who
