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The tumor arises in the pons, making surgical resection unfeasible and limiting treatment options to palliative radiation, which offers minimal survival benefit. One of the major challenges in treating DIPG is the poorly understood tumor immune microenvironment, which has hindered the development of effective immunotherapies. DIPG tumors are considered to be immunologically cold with limited immune cell infiltration. Recent studies have begun to reveal the complex and heterogeneous immune landscape of DIPG, highlighting distinct immunological subgroups. This review aims to provide a comprehensive overview of the immune landscape of DIPG based on the latest insights, identify research gaps, and suggest potential areas for future investigation to improve treatment outcomes for patients with DIPG.<\/jats:p>","DOI":"10.1136\/jitc-2025-012009","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:27Z","timestamp":1749772827000},"page":"e012009","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Exploring the tumor microenvironment in diffuse intrinsic pontine glioma: immunological insights and therapeutic challenges"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct04185038","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04196413","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5446-3510","authenticated-orcid":false,"given":"Bieke","family":"Van den Ende","sequence":"first","affiliation":[{"name":"Department of Oncology, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5962-5513","authenticated-orcid":false,"given":"Matteo","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Oncology, KU Leuven, Leuven, Belgium"},{"name":"Department of Neurosurgery, CHU UCL Namur, Yvoir, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6669-3335","authenticated-orcid":false,"given":"Frederik","family":"De 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