Tumor immune microenvironment in brain metastases from gynecologic malignancies

Introduction: The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens. Methods: We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection. Results: A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4⁺ TILs were evident in 76.9% of cases, CD8⁺ in 92.3%, CD45RO⁺ in 92.3%, and FOXP3⁺ in 46.2%, as well as CD68⁺ TAMs in 100% and CD163⁺ in 100%. For the 15 BM cases, CD4⁺ TILs were evident in 60.0% of cases, CD8⁺ in 93.3%, CD45RO⁺ in 73.3%, and FOXP3⁺ in 35.7%, as well as CD68⁺ TAMs in 86.7% and CD163⁺ in 100%. Conclusion: An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.