Role of myeloid cells in the immunosuppressive microenvironment in gliomas |
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| Affiliation: | 1. Humanitas Clinical and Research Center - IRCCS, Rozzano, Italy;2. Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy;3. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy;1. Singapore Immunology Network (SIgN), A*STAR, Singapore;2. Department of Microbiology and Immunology, National University of Singapore (NUS), Singapore, Singapore;1. Laboratorio de Oncología Experimental, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina;2. Laboratorio de Fisiología de los Procesos Inflamatorios, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina;3. Laboratorio de Inmunología Experimental, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina;1. Department of Pediatrics, Vittore Buzzi Children’s’ Hospital-University of Milan, Milan, Italy;2. Department of Pediatrics and Laboratory of Immuno-Allergology Foundation IRCCS Policlinico San Matteo, Pavia, Italy;3. Department of Pediatrics, University of Pavia Foundation IRCCS Policlinico San Matteo, Pavia, Italy;1. Department of Microbiology and Biotechnology, Max Rubner-Institut, Hermann-Weigmann-Str 1, D-24103, Kiel, Germany;2. Clinic of Dermatology, University Hospital Schleswig-Holstein, Schittenhelmstr. 7, D-24105 Kiel, Germany;3. Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein, Arnold-Heller-Straße 3/14, D-24105, Kiel, Germany;4. Städtisches MVZ Kiel GmbH (Kiel City Hospital), Department of Pathology, Chemnitzstr.33, 24116, Kiel, Germany;1. Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, China;2. Department of Emergency, Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, 712082, China;3. School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi, 712082, China;4. Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Northwest University, Xi’an, Shaanxi, 710069, China |
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| Abstract: | Glioma is the most common primary brain cancer, and half of patients present a diagnosis of glioblastoma (GBM), its most aggressive and lethal form. Conventional therapies, including surgery, radiotherapy, and chemotherapy, have not resulted in major ameliorations in GBM survival outcome, which remains extremely poor. Recent immunotherapy improvements for other tumors, coupled with growing knowledge of the complex interactions between malignant glioma cells and the immune system, led to an exponential increase in glioma immunotherapy research. However, immunotherapeutic strategies in GBM have not yet reached their full potential, mainly due to the limited understanding of the strong immunosuppressive microenvironment (TME) characterizing this tumor. Glioma-associated macrophages and microglia (GAMs) are key drivers of the local immunosuppression promoting tumor progression and its resistance to immunomodulating therapeutic strategies. Together with other myeloid cells, such as dendritic cells and neutrophils, GAMs actively shape glioma TME, modulate anti-tumoral immune response and support angiogenesis, tumor cell invasion and proliferation. In this review, we discuss the role of myeloid cells in the complex TME of glioma and the available clinical data on therapeutic strategies focusing on approaches that affect myeloid cells activity in GBM. |
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