"Warm up" the tumor
Despite the success of immunotherapy in the treatment of lung cancer or melanoma, it is still not very effective in "cold" breast cancer with low infiltration of immune cells.
Tumors use strategies to evade the immune system by reducing the infiltration of cells that can attack them, or by attracting immunosuppressive cells. These mechanisms worsen the prognosis in women with breast cancer, making them immune to immunotherapy. For this reason, a strategy that could transform immunologically "cold" tumors, in which immunotherapy is ineffective, into "warm" ones, will be an important step towards improving the effectiveness of immunological therapy for breast cancer.
In an article published in the journal Nature Communications, a group led by Eva Gonzalez-Suarez from the Bellwitge Biomedical Research Institute (IDIBELL) and the Spanish National Cancer Research Center (CNIO) demonstrates the potential of the RANK signaling pathway as a key candidate for modulating the immune response in breast tumors. In addition, in collaboration with Christos Sotiriou from the Jules Borde Institute in Belgium, the immunomodulatory activity of RANK has been confirmed in clinical studies involving premenopausal patients with luminal breast cancer – one of the most resistant to immunotherapy.
The study reports that inhibition of the RANK protein promotes the attraction of immune cells to the tumor in mouse models and in patients with breast cancer. In addition, tumors become more sensitive to immunotherapy after RANK inhibition in tumor cells. These results prove that the protein plays an important role in communication between tumor and immune cells.
A clinical study involving women with early stage breast cancer showed that patients tolerate the introduction of monoclonal antibodies that inhibit RANK well, demonstrating high treatment results: the infiltration of immune cells into the tumor increased. The researchers also identified biomarkers that will help select patients who are shown therapy with RANK inhibition.
The advantage of this work is that two independent studies, clinical and preclinical, have concluded that inhibition of RANK signaling enhances the antitumor immune response.
The monoclonal antibodies tested in this study are commonly used to treat bone diseases such as osteoporosis and bone metastases, but not to treat the primary tumor. The results obtained confirm the effectiveness of these antibodies in combination with breast cancer immunotherapy: the strategy can turn immunologically "cold" breast cancer into a tumor sensitive to the activity of the immune system.
Article by C.Gómez-Aleza et al. Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to CNIO: Scientists discover the immunomodulatory activity of a drug that would improve the efficacy of immunotherapy against breast cancer.