The results suggest that immunotherapy could be effective against tumors that have not previously shown any immune response, a step that could be transformative in the treatment of this disease, which accounts for about 70% of breast cancer cases and causes the highest mortality rate.
Typically, this type of tumor does not respond to immunotherapy due to the influence of estrogen receptors, which restrict immune cell infiltration and hinder the treatment's effectiveness. By analyzing data from multiple clinical trials, researchers found that inhibiting the estrogen receptor activates LCOR and interferon signaling, two factors that enhance antigen presentation on the cell surface, thus making the tumor visible to the immune system.
To confirm these findings, the team created a preclinical model in experimental animals and revealed that the estrogen receptor "blocks" the LCOR molecule, which has proven effective in enhancing immunotherapy against triple-negative breast cancer, and prevents it from performing its function.
To overcome this effect, the researchers used two strategies in a preclinical setting: first, combining LCOR with immunotherapy using hormone inhibitors already in place to treat this type of cancer; and second, developing a modified version of LCOR—LSKAA—that prevents its binding by estrogen receptors, thereby enhancing antigen presentation and facilitating the body’s response to immunotherapy.
"Using anti-estrogen therapy, LCOR can be activated and antigen presentation can be made, paving the way for immunotherapy," explains Jose Angel Palomeque, a researcher at the institute. "The modified version of LCOR avoids the effect of estrogen receptors and enhances the immune response."
In this context, the Institute’s RNA Therapy Generation Laboratory is working on developing modified LCOR therapies, while VIOLET Pharmaceuticals, a recent subsidiary, is focusing on developing this type of innovative therapy.
Dr. Joan Albanel, Chief of Medical Oncology and Director of the Cancer Research Program, says: "This study opens the door to a new strategy for stimulating the estrogen receptor-positive subtype of breast cancer to respond to immunotherapy, with the potential for these modified compounds to be developed into therapies that can be evaluated in future clinical trials."
