Over the past three decades, the treatment of malignant central nervous system (CNS) tumors has become increasingly challenging, with only a few therapeutic options currently approved. The growing recognition of the immune system’s role in the initiation, development, and progression of these tumors offers the potential for a more comprehensive treatment approach—one that could ultimately improve prognosis and survival rates. Immunotherapy, in particular, holds promise for positively influencing the tumor microenvironment by promoting a more favorable immune response. However, its impact has been limited by the lack of significant clinical responses compared to existing therapies for malignant brain tumors. This limitation is largely due to the complex interactions between tumor cells and infiltrating immune cells within the tumor microenvironment. Therefore, immunotherapy represents a promising avenue for improving outcomes in malignant CNS tumors, overcoming the barriers posed by the tumor microenvironment and the aggressiveness of the tumor itself.

The goal of this Research Topic is to provide a comprehensive overview of the latest immunotherapeutic strategies designed to modulate the antitumor immune response as well as tumor microenvironment. These approaches combine traditional biomedical research tools and new biotechnological advancements, including drug repurposing and the development of targeted therapies. A particular focus is placed on the tumor microenvironment, exploring its complex cellular and molecular components as both obstacles and opportunities for enhancing immunotherapy effectiveness. By targeting specific elements within the tumor microenvironment, these strategies aim to overcome immune resistance and improve treatment outcomes for patients with malignant CNS tumors.

The Editors of this Research Topic welcome the submission of Original Research articles, Reviews, Mini-Reviews and Bibliometric analyses focusing on emerging strategies to improve immunotherapy responses and to expand its scope and clinical applicability in the management of malignant brain tumors. We are especially interested in receiving papers aimed at, but not limited to:

• Immunotherapy response compared to current treatment
• Combination of current therapy with immunotherapeutic agents
• Limitations of immunotherapy
• Immunotherapy against carcinogenic stem cells
• Immunotherapy focused on tumor microenvironment modification
• Repurposing of agents with antitumor activity in combination with immunotherapy
• Proposals to redefine and broaden the targets of immunotherapy
• Tumor Microenvironment and its impact in survival

Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.

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Immunotherapy and Microenvironment in Malignant Central Nervous System Tumors