Under the direction of Maria Sibilia, a research team from the Medical University of Vienna has looked at a novel combination treatment for cancer. This treatment uses local application of imiquimod in conjunction with systemic delivery of the tissue hormone interferon-I. In models of breast cancer and melanoma, which are topically accessible malignancies, this combination had encouraging outcomes: Tumor cells at the treated areas died as a result of the therapy, which also triggered the adaptive immune system to combat even distant metastases. The findings, published in the prestigious journal Nature Cancer, may help treat surface malignancies including breast and melanoma.
Immunotherapies have been incredibly successful in treating and curing a variety of malignancies in recent years. However, these medications are still insufficiently effective for certain patients. Therefore, Maria Sibilia, Head of the Center for Cancer Research at the Medical University of Vienna, conducted a preclinical trial to examine the effects of a combination immunotherapy that included local imiquimod therapy and systemic infusion of the tissue hormone interferon (IFN)-I. Imiquimod is an active ingredient used to treat basal cell carcinomas that stimulates the innate receptors TLR7/8. Several preclinical mouse tumor models of breast cancer and melanoma were used by the researchers. Both tumors are amenable to local treatment, and they frequently spread to other locations.
Their findings were published in the journal Nature Cancer.
Immunotherapies combat cancer cells by utilizing the body’s immune system. Imiquimod activates plasmacytoid dendritic cells (pDCs) through TLR7/8, and these cells are crucial to this process. Oral imiquimod increases pDCs to release the tissue hormone IFN-I, according to the study. This made additional dendritic cells and macrophages in the tumor surroundings more sensitive to topical imiquimod therapy, which stopped the cytokine IL12 from forming new blood vessels, causing tumor cells to die.
The combination immunotherapy affected distant metastases in addition to the treated tumors. It increased the sensitivity of melanomas to checkpoint inhibitors and decreased the creation of new metastases, hence reducing malignant relapses.
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.
Maria Sibilia
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.
Philipp Novoszel
According to the findings, this therapeutic approach may help treat superficial and thus locally accessible tumors like breast cancer and melanoma. This is due to the fact that checkpoint inhibitors can enhance the T cell-induced anti-tumor immune response at distant metastases, in addition to therapy-associated cancer cell death at locally treated tumors.
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.
Maria Sibilia
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.
Martina Sanlorenzo
Source: Medical University of Vienna – News
Journal Reference: Sanlorenzo, Martina, et al. “Systemic IFN-I Combined with Topical TLR7/8 Agonists Promotes Distant Tumor Suppression by C-Jun-dependent IL-12 Expression in Dendritic Cells.” Nature Cancer, 2025, pp. 1-19, DOI: https://doi.org/10.1038/s43018-024-00889-9.
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Graduated from the University of Kerala with B.Sc. Botany and Biotechnology. Attained Post-Graduation in Biotechnology from the Kerala University of Fisheries and Ocean Science (KUFOS) with the third rank. Conducted various seminars and attended major Science conferences. Done 6 months of internship in ICMR – National Institute of Nutrition, Hyderabad. 5 years of tutoring experience.
