Central nervous system immune interactome is a function of cancer lineage, tumor microenvironment, and STAT3 expression

BACKGROUND. Immune cell profiling of primary and metastatic CNS tumors has been focused on the tumor, not the tumor microenvironment (TME), or has been analyzed via biopsies. METHODS. En bloc resections of gliomas (n = 10) and lung metastases (n = 10) were analyzed via tissue segmentation and high-dimension Opal 7-color multiplex imaging. Single-cell RNA analyses were used to infer immune cell functionality. RESULTS. Within gliomas, T cells were localized in the infiltrating edge and perivascular space of tumors, while residing mostly in the stroma of metastatic tumors. CD163(+) macrophages were evident throughout the THE of metastatic tumors, whereas in gliomas, CD68(+), CD11c(+)CD68(+), and CD11C(+)CD68(+)CD163(+) cell subtypes were commonly observed. In lung metastases, T cells interacted with CD163(+) macrophages as dyads and clusters at the brain-tumor interface and within the tumor itself and as clusters within the necrotic core. In contrast, gliomas typically lacked dyad and cluster interactions, except for T cell CD68(+) cell dyads within the tumor. Analysis of transcriptomic data in glioblastomas revealed that innate immune cells expressed both proinflammatory and immunosuppressive gene signatures. CONCLUSION. Our results show that immunosuppressive macrophages are abundant within the THE and that the immune cell interactome between cancer lineages is distinct. Further, these data provide information for evaluating the role of different immune cell populations in brain tumor growth and therapeutic responses.