Central nervous system (CNS) metastases are the most common type of brain tumors and cause grave morbidity and quality of life deterioration in patients with advanced systemic malignancies. CNS metastases involve metastatic spread to the brain parenchyma, dura and leptomeninges. The most common solid tumors that are origin of CNS metastasis are lung cancer, breast cancer and melanoma, including both brain metastases and leptomeningeal disease, but almost all malignancies can develop them, including lymphomas. Leptomeningeal spread occurs in both solid and hematologic malignancies. The incidence of brain metastases is increasing owing to a longer survival of patients and better control of systemic disease with new treatments. CNS metastases confer poor prognosis and depends on age, performance status, burden of systemic disease, number, and location of brain metastases among others.
Treatment options are surgical resection, stereotactic radiosurgery, whole-brain radiation, and systemic antineoplastic drugs. Most traditional chemotherapies have shown limited activity in CNS because of the blood-brain barrier and the molecular structure of the chemotherapeutic agents. In some tumors, the discovery of driver mutations have extended treatment armamentarium with the development of small-molecule tyrosine-kinase inhibitors (TKI) targeting these mutations. Several of these targeted small-molecular TKIs do cross the blood-brain barrier and have activity in CNS. Another major advance in oncology has been the development of cancer immunotherapy and some studies have already shown intracranial activity of immunotherapeutic agents.
However , it is a complex issue, since brain immunology is different from the immune system elsewhere. On the one hand, blood-brain-barrier plays an important role in limiting the entrance of immune agents into the brain, leading to an immunosuppressive environment. On the other hand, intracranial tumors have specific immune microenvironment with heterogenous properties mainly composed of microglia and astrocytes that is overall immunosuppressed, which is a major challenge for immunotherapy. Nonetheless, brain metastases immune microenvironment is still a topic under investigation and there are several immunotherapeutic strategies that are being investigated to fight them.
In this Research Topic, we aim to explore the immune microenvironment of CNS metastases and the immunotherapeutic strategies that are being tried and developed to use in the treatment of central nervous system metastases. We welcome submissions of Original Research, Review Articles, Perspectives, Short Reports, and Mini-Reviews, covering, but not limited to, the following subtopics:
1. Process and mechanisms of brain metastasis.
2. Basic research about the components and features of immune microenvironment of central nervous system metastases.
3. Immune microenvironment of central nervous system metastases from different primary tumours.
4. New clinical studies focusing on immunotherapy in patients with brain metastases.
5. Novel immunotherapeutic drugs and strategies against brain metastases.
6. Development of ICI-based combinational therapy in patients with brain metastases.
7. Combination of radiotherapy and immunotherapy in the treatment of brain metastases.
8. Potential biomarkers for predicting therapeutic and prognostic value in patients with brain metastases and immunotherapy.
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 topic.
Topic Editor Xabier Mielgo-Rubio received financial support from Brystol Myers Squibb. Topic Editor Felipe Couñago received financial support from Janssen, AstraZeneca, Astellas, Roche Farma. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Central nervous system (CNS) metastases are the most common type of brain tumors and cause grave morbidity and quality of life deterioration in patients with advanced systemic malignancies. CNS metastases involve metastatic spread to the brain parenchyma, dura and leptomeninges. The most common solid tumors that are origin of CNS metastasis are lung cancer, breast cancer and melanoma, including both brain metastases and leptomeningeal disease, but almost all malignancies can develop them, including lymphomas. Leptomeningeal spread occurs in both solid and hematologic malignancies. The incidence of brain metastases is increasing owing to a longer survival of patients and better control of systemic disease with new treatments. CNS metastases confer poor prognosis and depends on age, performance status, burden of systemic disease, number, and location of brain metastases among others.
Treatment options are surgical resection, stereotactic radiosurgery, whole-brain radiation, and systemic antineoplastic drugs. Most traditional chemotherapies have shown limited activity in CNS because of the blood-brain barrier and the molecular structure of the chemotherapeutic agents. In some tumors, the discovery of driver mutations have extended treatment armamentarium with the development of small-molecule tyrosine-kinase inhibitors (TKI) targeting these mutations. Several of these targeted small-molecular TKIs do cross the blood-brain barrier and have activity in CNS. Another major advance in oncology has been the development of cancer immunotherapy and some studies have already shown intracranial activity of immunotherapeutic agents.
However , it is a complex issue, since brain immunology is different from the immune system elsewhere. On the one hand, blood-brain-barrier plays an important role in limiting the entrance of immune agents into the brain, leading to an immunosuppressive environment. On the other hand, intracranial tumors have specific immune microenvironment with heterogenous properties mainly composed of microglia and astrocytes that is overall immunosuppressed, which is a major challenge for immunotherapy. Nonetheless, brain metastases immune microenvironment is still a topic under investigation and there are several immunotherapeutic strategies that are being investigated to fight them.
In this Research Topic, we aim to explore the immune microenvironment of CNS metastases and the immunotherapeutic strategies that are being tried and developed to use in the treatment of central nervous system metastases. We welcome submissions of Original Research, Review Articles, Perspectives, Short Reports, and Mini-Reviews, covering, but not limited to, the following subtopics:
1. Process and mechanisms of brain metastasis.
2. Basic research about the components and features of immune microenvironment of central nervous system metastases.
3. Immune microenvironment of central nervous system metastases from different primary tumours.
4. New clinical studies focusing on immunotherapy in patients with brain metastases.
5. Novel immunotherapeutic drugs and strategies against brain metastases.
6. Development of ICI-based combinational therapy in patients with brain metastases.
7. Combination of radiotherapy and immunotherapy in the treatment of brain metastases.
8. Potential biomarkers for predicting therapeutic and prognostic value in patients with brain metastases and immunotherapy.
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 topic.
Topic Editor Xabier Mielgo-Rubio received financial support from Brystol Myers Squibb. Topic Editor Felipe Couñago received financial support from Janssen, AstraZeneca, Astellas, Roche Farma. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
