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Over the years, the heterogeneous and adaptive nature of GBM has been highlighted as a major contributor to the poor efficacy of many treatments including various immunotherapies. The major challenge lies in understanding and manipulating the complex interplay among the different components within the tumor microenvironment (TME). This interplay varies not only by the type of cells interacting but also by their spatial distribution with the TME. This review highlights the various immune and non-immune components of the tumor microenvironment and their consequences f the efficacy of immunotherapies. Understanding the independent and interdependent aspects of the various sub-populations encapsulated by the immune and non-immune components will allow for more targeted therapies. Meanwhile, understanding how the TME creates and responds to different environmental pressures such as hypoxia may allow for other multimodal approaches in the treatment of GBM. Ultimately, a better understanding of the GBM TME will aid in the development and advancement of more effective treatments and in improving patient outcomes.<\/jats:p>","DOI":"10.3390\/cells10092257","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T08:42:32Z","timestamp":1630399352000},"page":"2257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["The Interplay between Glioblastoma and Its Microenvironment"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-2373","authenticated-orcid":false,"given":"Mark","family":"Dapash","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"},{"name":"Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandyn","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"},{"name":"Department of Neurosurgery, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Lee-Chang","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0096-5107","authenticated-orcid":false,"given":"Maciej S.","family":"Lesniak","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Vleeschouwer, S. 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