Results from a preclinical study in mice, led by EPFL, and a collaborative clinical study in patients show that the type 2 immune response is positively correlated with long-term cancer remission. The study, published in Nature, involved analyzing CAR-T cells from ALL patients, including Emily Whitehead, who had undergone innovative CAR-T therapy. Researchers found that patients who had a type 2 immune response, characterized by the presence of proteins like IL-4, showed a statistically significant correlation with eight-year relapse-free remission from ALL.
In CAR-T therapy, T cells are engineered to target a patient’s cancer and then transferred back into the patient. The researchers analyzed nearly 700,000 CAR-T cells from 82 ALL patients and six healthy controls to create a gene expression atlas. They found that the cells of long-term survivors contained certain proteins associated with a type 2 immune response, traditionally thought to be ineffective in fighting cancer. However, the data showed that type 2 immune factors like IL-4 could play a positive role in cancer immunity and promote long-term remission from ALL.
A second study, led by Li Tang’s lab at EPFL and published in Nature, investigated the mechanism of type 2 immunity by comparing the effects of type 1 CAR-T immunotherapy alone with a combined type 1/type 2 immunotherapy on tumors in mice. The combined therapy, which included a modified version of the IL-4 cytokine, resulted in a greater curative response rate (86%) and improved survival even after the mice’s immune systems were re-challenged with cancer cells. The modified IL-4 appeared to be promoting glycolysis, providing an energy boost to T cells and enhancing their ability to fight cancer.
By harnessing type 2 immunity to enhance current immunotherapy, researchers have discovered a potential strategy for advancing next-generation cancer treatment. The study suggests that type 1 and type 2 immunity can work synergistically to fight cancer, challenging the traditional type 1-centric approach to cancer immunotherapy. The results from both the preclinical and clinical studies may inspire further research in the field to explore the role of type 2 immunity and reconsider the existing paradigm in cancer treatment.
The findings from these studies offer new insights into the potential benefits of type 2 immune response in cancer remission and immunotherapy. While the results are correlational and do not establish a causal relationship, the data suggest that type 2 immune factors like IL-4 can reinvigorate T cells and enhance their ability to combat cancer. By integrating type 2 immune factors into current immunotherapy approaches, researchers hope to develop more effective treatments for cancer patients and improve long-term outcomes in cancer remission. These studies pave the way for further research into the role of type 2 immunity in cancer therapy and encourage a reevaluation of the current treatment strategies in the field.