Blockade of Na/H exchanger stimulates glioma tumor immunogenicity and enhances combinatorial TMZ and anti-PD-1 therapy
| العنوان: | Blockade of Na/H exchanger stimulates glioma tumor immunogenicity and enhances combinatorial TMZ and anti-PD-1 therapy |
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| المؤلفون: | Wang Jia, Maria G. Castro, Gary Kohanbash, Anders Persson, Xiudong Guan, Karen E. Carney, Victoria M. Pigott, Gulnaz Begum, Dandan Sun, Nabiul Hasan |
| المصدر: | Cell Death and Disease, Vol 9, Iss 10, Pp 1-16 (2018) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, medicine.medical_treatment, Immunology, Programmed Cell Death 1 Receptor, Article, Antibodies, Proinflammatory cytokine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, 0302 clinical medicine, Glioma, Cell Line, Tumor, medicine, Temozolomide, Tumor Microenvironment, Cytotoxic T cell, Animals, lcsh:QH573-671, Cell Proliferation, Tumor microenvironment, Sodium-Hydrogen Exchanger 1, Chemistry, lcsh:Cytology, Immunogenicity, Macrophages, Cell Biology, Immunotherapy, medicine.disease, 3. Good health, Blockade, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Female, Microglia, medicine.drug, T-Lymphocytes, Cytotoxic |
| الوصف: | The weak immunogenicity of gliomas presents a barrier for effective immunotherapy. Na/H exchanger isoform 1 (NHE1) maintains alkaline intracellular pH (pHi) of glioma cells and acidic microenvironment. In addition, NHE1 is expressed in tumor-associated microglia and tumor-associated macrophages (TAMs) and involved in protumoral communications between glioma and TAMs. Therefore, we hypothesize that NHE1 plays a role in developing tumor resistance and immunosuppressive tumor microenvironment. In this study, we investigated the efficacy of pharmacological inhibition of NHE1 on combinatorial therapies. Here we show that temozolomide (TMZ) treatment stimulates NHE1 protein expression in two intracranial syngeneic mouse glioma models (SB28, GL26). Pharmacological inhibition of NHE1 potentiated the cytotoxic effects of TMZ, leading to reduced tumor growth and increased median survival of mice. Blockade of NHE1 stimulated proinflammatory activation of TAM and increased cytotoxic T cell infiltration into tumors. Combining TMZ, anti-PD-1 antibody treatment with NHE1 blockade significantly prolonged the median survival in the mouse glioma model. These results demonstrate that pharmacological inhibition of NHE1 protein presents a new strategy for potentiating TMZ-induced cytotoxicity and increasing tumor immunogenicity for immunotherapy to improve glioma therapy. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b7c18832ad3e00559cdd0a6c4d97eb9f http://link.springer.com/article/10.1038/s41419-018-1062-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b7c18832ad3e00559cdd0a6c4d97eb9f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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