Background: Programmed death-ligand 1 (PD-L1) plays important roles in the evasion of antitumor immunity. Because we observed the localization of PD-L1-positive (PD-L1⁺) cells in the marginal region of triple-negative breast cancer (TNBC) specimens, we hypothesized that the marginal microenvironment of TNBC would involve the induction of PD-L1⁺ cells. Methods: One hundred and one TNBC surgical specimens were examined. We performed immunohistochemical (IHC) studies of PD-L1, CD68, CD8, and pan-cytokeratin in these specimens. We analyzed the localization of IHC-positive cells and the distance between these cells by histological spatial analysis. Results: In 30.7% of TNBC specimens, PD-L1⁺ cells were located in the marginal region. Approximately three PD-L1⁺ cells accumulated around a single TNBC cell. Most PD-L1⁺ cells were located within 50 μm of TNBC cells. PD-L1⁺ cells were indicated to interact with TNBC cells in the marginal region. PD-L1⁺CD68⁺ cells were located in the marginal region, while CD68⁺ macrophages (MΦs) were observed either in the marginal region or the core region. PD-L1 expression in MΦs was induced in the marginal region. The colocalization of CD8⁺ T cells in the marginal region indicates that PD-L1 expression in MΦs would be induced by interaction with CD8⁺ T cells. Because CD8⁺ T cells are positive for CCL2, CCL2 may induce PD-L1 expression in MΦs. Conclusion: At the marginal microenvironment of TNBC, PD-L1 expression would be induced in MΦs by interaction with CD8⁺ T cells through CCL2. The interaction between PD-L1⁺ MΦs and TNBC cells would facilitate the growth of TNBC under antitumor immunity. These interactions would be potential targets for restoring antitumor immunity and suppressing TNBC progression.

Background/Objectives: Meningiomas frequently involve the adjacent skull bone. The bone tumor microenvironment (TME) represents a unique niche in bone-invasive tumors and bone metastases, and can promote tumor progression through tumor–stromal interactions. We hypothesized that the bone TME may contribute to tumor cell transcriptional changes and tumor growth in meningioma. Methods: Human malignant meningioma cell lines, IOMM-Lee and HKBMM, were implanted over the calvarial bone (bone TME) and into the dorsal skin (non-bone TME) of BALB/c-nu/nu mice. Tumors from the IOMM-Lee model underwent bulk RNA sequencing with computational separation of human- and mouse-derived reads, enabling ligand–target interaction analysis of stromal cell-to-tumor cell signaling. Differential gene expression analysis, enrichment analysis, ligand–target interaction analysis, multiplex immunofluorescence, and immunohistochemistry were performed. Results: Tumor volume was significantly greater in the bone TME than in the non-bone TME in both models, whereas the Ki-67 labeling index was significantly reduced. Transcriptomic analysis revealed distinct tumor cell transcriptional states in the bone TME, characterized by upregulation of inflammation-related genes and enrichment of inflammatory signaling pathways, including interferon responses and NF-κB signaling. Ligand–target interaction analysis of stromal cell-to-tumor cell signaling identified stromal IL1B as a candidate regulator of inflammatory transcriptional programs in tumor cells. F4/80-positive macrophages expressed IL-1β, and tumor cells were positive for phospho-IKKα/β and phospho-IκBα in the bone TME. Conclusions: Tumor–stromal interactions potentially involving macrophage-derived IL-1β may be associated with inflammatory transcriptional programs in meningioma cells and with meningioma enlargement in the bone TME. These interactions may be therapeutically relevant in meningioma with bone involvement.