Research develops new ways to make cancer treatment safer
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Cancer immunotherapy, as a treatment method to eliminate cancer by mobilizing the cancer patient's own immune system and enhancing the function of immune cells, has caused waves of heat waves around the world. Among them, immune checkpoint inhibitors (PD-1/PD-L1 inhibitors, etc.) and cell therapy (CAR-T cell therapy, etc.) are the most popular.
While combination immunotherapy with anti-PD-1 and anti-CTLA-4 agents has transformed the treatment of many cancer types, patients who respond to combination immunotherapy often also experience significant side effects. The data showed that the overall incidence of hospitalization for immune-related adverse events was 3.5% per year, of which 3.3% were treated with PD-1 inhibitors and 1.1% were treated with PD-L1 inhibitors; CTLA-4 3.9% of patients received inhibitor therapy and 7.3% received combination therapy.
Such a high incidence of side effects places a great burden on patients. To address this issue, researchers at The University of Texas MD Anderson Cancer Center have developed a unique technology that reduces the effects of immunotherapy by targeting the cytokine interleukin-6 (IL-6). immune side effects.
IL-6 is a pleiotropic cytokine with a wide range of functions, which can regulate the growth and differentiation of various cells, and has the functions of regulating immune response, acute phase response and hematopoiesis. There are many target cells that IL-6 acts on, including macrophages, hepatocytes, quiescent T cells, activated B cells, and plasma cells. Its biological effects are also very complex and play an important role in the body's anti-infection immune response.
By observing patients who received immunotherapy, the researchers found that IL-6 and Th17 were up-regulated in inflamed tissues and normal tissues with different immune signatures. In addition, the IL-6 gene signature was increased in patients whose tumors did not respond to immunotherapy, but this change was not present in responders.
Based on this, the researchers used several preclinical models to evaluate the effects of IL-6 blockade on autoimmunity and response to anti-CTLA-4 therapy. The results showed that the combination of an IL-6 blockade with an immune checkpoint inhibitor reduced experimental autoimmune encephalomyelitis (EAE) symptoms and improved tumor control.
To test this finding, the researchers then performed a retrospective analysis of 31 melanoma patients who started IL-6 blockade an average of 3.7 months after their adverse effects. It was found that symptoms related to side effects were reduced by 74% after about two months of treatment. This suggests that the combination of IL-6 blockade and immune checkpoint inhibitor can indeed suppress the inflammatory response and may enhance antitumor immunity.
In the future, it is hoped that this therapy can effectively improve the side effects of immunotherapy in clinical applications.