About this Research Topic

Background

Conventionally, metastases are treated using different combinations of surgery, radiotherapy, and systemic therapy. Nevertheless, survival amongst patients suffering metastatic spread to the brain remains extremely poor. Treatment failure frequently reflects the impact of complex and variable factors within the unique brain microenvironment, resulting in resistance to therapy and the onset of an immunosuppressive tumor microenvironment (TME). Thus, the development of new therapeutic strategies targeting brain-specific TME components has become one of the biggest challenges in the field. Furthermore, owing to the complexity of brain metastasis and the unique environment of the brain, a combination approach is now thought most likely to confer successful treatment of brain metastases.

Brain metastases are heterogeneous, consisting of a broad panel of different cancer subtypes. It is unlikely, therefore, that no single therapy will be efficacious across all subtypes of brain metastasis. Moreover, the combination of treatments may greatly decrease the probability of developing therapy resistance. It is becoming clear that the immune response to brain metastasis evolves over the time course of tumor progression, and can have both tumor-suppressive and tumor-promoting effects. Generally, however, conventional therapies such as radiotherapy, chemotherapy, and glucocorticoid therapy are independently immunosuppressive. Therefore, a thorough understanding of the TME in brain metastasis and its response to different therapeutic strategies are essential for the successful development of novel strategies to improve outcomes for patients with metastatic spread to the brain.

Thus, the overarching goal of this Research Topic is to discuss the current state of knowledge with regards to the immune response to brain metastasis, with a primary focus on individual components of the brain immune response and TME, novel immunotherapeutic approaches or combinations of therapies, challenges, and solutions to overcoming
therapeutic access across the blood-brain barrier and interactions between radiotherapy and immunotherapy in brain metastasis. Additional areas that may be included are targeting of immune biomarkers for improved diagnosis or treatment planning.

We aim at pursuing Original Research articles, Perspective, and Reviews accounting for the current state of brain metastasis studies. Principally, we would like to address the following topics:
- Components of the brain immune response (endothelium, macrophages, astrocytes): pro- or anti-tumorigenic?
- Immunotherapy: novel approaches to modulating the immune response to brain metastasis.
- The innate brain hurdle: challenges and novel strategies to crossing the blood-brain barrier.
- Therapy resistance: is the immune response a major player?
- Radiotherapy: enhancing the immunogenicity of brain metastasis.
- Novel biomarkers; improving diagnosis and treatment planning by targeting immune markers.

Keywords: brain metastasis, immune response, brain microenvironment, immunotherapy, biomarkers

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