Comparison of the tumor immune microenvironment between glioblastoma and metastatic brain tumors.

Abstract

Background: Brain metastases (BrM), which commonly arise in patients with melanoma, breast cancer and lung cancer, are associated with a poor clinical prognosis. In this context, the tumor microenvironment (TME) plays an important role since it either promotes or inhibits tumor progression. Our previous studies have characterized the immunosuppressive microenvironment of glioblastoma (GBM). The aim of this study is to compare the immune profiles of BrM and GBM in order to identify potential differences that may be exploited in their differential treatment. Methods: Tumor and/or blood samples were taken from 20 BrM patients and 19 GBM patients. Multi-parametric flow cytometry was used to evaluate myeloid and lymphoid cells, as well as the expression of immune checkpoints in the TME and blood. The Mann-Whitney test and t-test were utilized for statistical analysis. Results: High frequencies of myeloid cells dominate both the BrM and GBM landscapes, but there is a higher presence of tumor-associated macrophages in GBM, while BrM are characterized by a significant presence of tumor-infiltrating lymphocytes. Exhaustion markers are highly expressed in all T cells from both primary and metastatic brain tumors. The cell cycle analysis of a BrM and a GBM revealed proliferating tumor cells and blood-derived macrophages, but quiescent lymphocytes and resident microglial cells. As previously demonstrated for GBM, macrophages sorted from a lung BrM exhibited a strong immunosuppressive activity. Finally, a significant expansion of some myeloid cell subsets was observed in the blood of both GBM and BrM patients. Conclusions: Our results define the main characteristics of the immune profile of BrM and GBM, which are distinguished by different levels of immunosuppressive myeloid cells and lymphocytes devoid of effector function. Understanding the role of the different cells in establishing the metastatic setting is critical to improving the therapeutic efficacy of new targeted immunotherapy strategies.