Brain metastases are common intracranial neoplasms and their frequency increases with prolonged survival of cancer patients. New pharmaceuticals targeting oncogenic kinases and immune checkpoint inhibitors augment both overall and progression-free survival in patients with brain metastases, but are not fully successful in reducing metastatic burden and still a majority of oncologic patients die due to dissemination of the disease. Despite therapy advancements, median survival of patients with brain metastases is several months, although it may vary in different types or subtypes of cancer. Contribution of the innate immune system to cancer progression is well established. Tumor-associated macrophages (TAMs), instead of launching antitumor responses, promote extracellular matrix degradation, secrete immunosuppressive cytokines, promote neoangiogenesis and tumor growth. While their roles as pro-tumorigenic cells facilitating tissue remodeling, invasion and metastasis is well documented, much less is known about the immune microenvironment of brain metastases and roles of specific immune cells in those processes. The central nervous system (CNS) is armed in resident myeloid cells: microglia and perivascular macrophages which colonize CNS in early development and maintain homeostasis in brain parenchyma and at brain-blood vessels interfaces. In this study we discuss available data on the immune composition of most common brain metastases, focusing on interactions between metastatic cancer cells and microglia, perivascular and meningeal macrophages. Cancer cells ‘highjack’ several CNS protective mechanisms and may employ microglia and CNS-border associated macrophages into helping cancer cells to colonize a pre-metastatic niche. We describe emerging molecular insights into mechanisms governing communication between microglia and metastatic cancer cells that culminate in activation of CNS resident microglia and trafficking of monocytic cells from the periphery. We present mechanisms controlling those processes in brain metastases and hypothesize on potential therapeutic approaches. In summary, microglia and non-parenchymal brain macrophages are involved in multiple stages of a metastatic disease and, unlike tumor cells, are genetically stable and predictable, which makes them an attractive target for anticancer therapies.

Glioblastoma (GBM) is the most common and most aggressive type of primary brain tumour in adults. It represents 54% of all gliomas and 16% of all brain tumours (Ostrom et al. 2016). Despite surgery and treatment with radiotherapy plus an oral alkylating agent, temozolomide (TMZ), tumours invariably recur, and the patient survival is an average of ~14–16 months. In this review we summarise the current understanding of multiple factors that may affect survival of patients with GBMs. In particular, we discuss recent advancements in surgery and detection of genomic-based markers with prognostic values, such as IDH1/2 mutations, MGMT gene promoter methylation, and TERT gene promoter alterations. We address the issue of tumour heterogeneity and evolution that may result in different parts of the same tumour exhibiting different GBM subtypes and in subtype switching, which may restrict the usefulness of the expression-based classification as a prognostic marker before relapse. The determinants of long-term survival in patients with IDH1/2wt GBM, beyond MGMT promoter methylation, remain to be identified, and even the absence of both IDH1/2 mutations and MGMT promoter methylation does not preclude long-term survival. These findings suggest that host-derived factors, such as immune system responsiveness may contribute to long-term survival in such patients. We report the results of high-throughput approaches, suggesting links between long-term survival and enhanced immune-related gene expression. The further search for new gene candidates, promoter methylation status, and specific features of host immunity should provide prognostic biomarkers for the evaluation of survival of IDH1 wild-type/non-G-CIMP GBMs.

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Purpose Surgical series of pineal region gliomas are rarely available. Whereas it is a general assumption that the extent of surgical resection correlates with survival outcomes of intracranial gliomas; the impact of the microsurgical resection on the long-term outcomes of pineal gliomas has been questioned. We present a surgical series of pineal region gliomas with focus on the survival outcome analysis. Methods 17 histologically confirmed pineal region glioma patients classified as diffuse and non-diffuse gliomas were retrospectively analyzed. A detailed description of the series was followed by regression models to identify predictors of clinical outcomes. Uni- a multivariate survival analysis was performed to determine independent predictors of mortality. Results Although the number of treated patients was small, only WHO grade histopathology remained significant (p = 0.02) after multivariate survival analysis with extent of resection, age, tumor volume, and preoperative functional status. The extent of the surgical resection did not correlate with the disease survival rates of non-diffuse (p = 1), diffuse (p = 0.2), nor all gliomas (p = 0.6). 15 of 17 patients underwent gross total (nine patients) or subtotal resection. The preoperative functional status of the patients showed overall improvement on the immediate (p < 0.001) and long-term (p = 0.03) follow-up after 106 (3 – 324) months. Conclusion The extent of the surgical resection does not seem to significantly impact on the survival outcomes of pineal region gliomas. Thus, genotype and molecular features may essentially affect the outcome. Further research on the field is required. Electronic supplementary material The online version of this article (10.1007/s11060-020-03571-z) contains supplementary material, which is available to authorized users.