Researchers at St. Jude Children’s Research Hospital have discovered a new way to treat cancer using immunotherapy without having autoimmune or inflammatory complications. What is interesting is that the mechanism that was tested on laboratory animals is present also in humans. Researchers have focused on regulatory T cells, cells belonging to the immune system. These cells control processes of autoimmunity and inflammation and also interfere with the immune system’s ability to fight cancer.
The study led by researchers at St. Jude Children’s Research Hospital shows that there is a mechanism that stimulates the ability of regulatory T cells to cause complications by blocking an effective anti-tumor immune response. What is noteworthy is that the same process does not cause the immune system to attack self healthy tissues, ie to produce autoimmune or inflammatory complications. Researchers have demonstrated that blocking this mechanism leads to the destruction of melanoma in rats without causing complications (such as other autoimmune diseases, as it happens in standard treatments currently used).
Dario Vignali, Ph.D., vice chair of the St. Jude Department of Immunology, said that regulatory T cells are a barrier to effective antitumor immunity and that their study identified a mechanism that stimulates regulatory T cells’ ability to destroy tumors without interfering with autoimmunity processes. Vignali explained that this is for the first time when they are able to selectively target the activity of regulatory T cells in cancer therapy without inducing autoimmunity and other inflammatory diseases.
The mechanism identified by researchers at St. Jude Children’s Research Hospital involves two proteins: semaphorin-4a (Sema4a) and neuropilin-1 (Nrp1); the first is found on the surface of many immune cells, while the second is found on the surface of regulatory T cells. The researchers used several techniques to demonstrate that the binding of Nrp1 to Sema4a activates a signaling pathway that stimulates regulatory T cells. When researchers removed Nrp1 only on regulatory T cells, those cells did not respond to signals that normally support their anti-inflammatory activity. Reseachers said that this mechanism is present also in humans.
The researchers explained that after 16 months of Nrp1 removal, there were no complications such as autoimmune or inflammatory diseases. Vignali pointed out that this is extremely important because those who have defects in regulatory T cells have an increased risk of developing fatal autoimmune disease. For the first time, we may now have an opportunity to selectively target the activity of regulatory T cells for treatment of cancer without inducing autoimmune or inflammatory complications “, said Vignali.