Nat Neuro: New immunotherapy combination may be effective in treating pediatric brain cancer

Introduction: Oncologists know that "chemotherapy and radiotherapy" is one of the preferred anti-cancer therapiesBecause the combination of chemotherapy can kill cancer cells more effectivelyHowever, for children with cancer, their weak bodies are still growing and their organs are not yet fully developedThose who use routine cancer therapy in adults in children are likely to cause lifelong damage, even loss of seine, and poor quality of lifeThis is not alarmist or exaggeratedThis is especially true in children with physical tumorsPhysicians and researchers working with neurotsis doctors and researchers in children around the world are trying to find effective treatments for cancer, while at the same time reducing the side effects of treatment and preserving the normal growth and development of childrenscientists at the Sanford Burnham Prebys (SBP) Institute of Medical Discovery have found that combining immunotherapy with a drug called tumor necrosis factor (TNF) can eliminate a deadly pediatric brain tumor in mice,The findings, published in Nature Neuroscience, are expected to lead to a clinical trial to test the benefits of the treatment for patientsThe findings also affect other cancers that do not respond to immunotherapyMany immunotherapy sits by enhancing the ability of cytotoxic T cells to kill tumor cellsKilling depends on T-cell recognition of the antigen of the antigen presented with the Class I major tissue compatibility complex (MHC-1) protein on tumor cellsThis study shows that myeloma tumors that lack p53 tumor inhibitors do not express surface MHC-1 and are therefore resistant to immune rejectionMechanically, this is because p53 regulates the expression of the peptide-transfer protein Tap1 and aminopeptide Erap1 required for MHC-1 transfer to the cell surfacein vitro, tumor necrosis factor (TNF) or lymphtoxin-beta receptor agonists can save the expression of Erap1, Tap1 and MHC-1 on p53 mutant tumor cellsIn the body, low doses of TNF can prolong survival and work with immunocheckpoint inhibitors to promote tumor rejection These studies have identified p53 as a key regulator for immune escape and suggest that TNF can be used to increase tumor sensitivity to immunotherapy senior author of the paper, director of the SBP Neuro-Oncology Research Center, and program director of the Joseph Cleese III Center for Neuro-Oncology and Genomics at the Radhi Institute for Child Genomicmedicine (RCIGM), Dr Robert Wechsler-Reya, who has studied myelin cell tumors for more than 20 years He has seen many therapies that improve survival in mice But this is the first time he has seen a treatment that can completely disappear the tumor They look forward to testing the method at the clinic and hope the discovery will save the child's life Robert Wechsler-Reya, PhD, author of the paper, and , director of the SBP Center for Neuro-Oncology Research, a quarter of children cannot survive myeloma, and that a tumor with a mutation of p53, a protein that blocks tumor growth, is particularly deadly The standard treatments for the disease are surgery, whole brain and spinal radiation, and intensive chemotherapy Although these positive treatments can cure some patients, surviving patients often suffer devastating long-term side effects, including intellectual disabilities, hormonal imbalances, and an increased risk of cancer later in life Scientists have been working on immunotherapy, which uses an individual's immune system to destroy cancer and is a safer and more effective treatment for myelin cell tumors "We are very encouraged by these findings and hope to be conducted as soon as possible," said Dr Sabine Mueller, co-founder of the Pacific Children's Neurotumor Alliance (PNOC), a network of children's hospitals that provide personalized treatment for children and young people with brain tumours Chemotherapy and radiotherapy are difficult for adults, especially in children For these vulnerable pediatric patients, treatment is not progressing fast enough invisibility cloak to remove tumors
In this study, Cherch Rea and his colleagues conducted a series of experiments to study why two different mouse models of myelin tumors (one with p53 mutation and the other without a different immune response between the p53 mutations) p53, commonly referred to as the "genome guardian," scans for errors in DNA and is the most common mutant gene in human cancer these experiments showed that tumors lacking p53 did not show important proteins on their surfaces, called major tissue compatibility complex I (MHC-1) MHC-1 makes tumors recognized and killed by the immune system Without it, tumors are invisible to the immune system and continue to grow scientists have found that low-dose TNF can increase the expression of MHC-1 on p53 mutated tumors, eliminating their "invisibility cloak" and causing it to be detected and destroyed by the immune system Importantly, when mice with p53 mutations receive both TNF and an immunotherapy called immunodeficiency inhibitors, the tumor disappears completely this work shows that adding TNF to immunotherapy can benefit myeloma patients with p53-deficient tumors In the absence of p53, low doses of TNF may raise MHC-1 to the level required for immunotherapy to work scientists also tested the combination therapy in a mouse model of diffuse endogenous cerebral bridge glioma (DIPG), a deadly pediatric brain tumor with a mortality rate of nearly 100 percent After treatment, about half of these mice survived cancer studies have shown that some cancers may not respond to immunotherapy because the MHC-I levels of these tumors are not sufficient to trigger an effective immune response Their hope is that, in the short term, combining immunotherapy with TNF will improve the effectiveness of immunotherapy for children with brain cancer