Cellular architecture of human brain metastases

The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis

“…5c ). To understand the mechanism of immune modulation by the TBME, we compared the expression of regulatory genes mediating: (1) T-cell activation or inhibition, which plays a critical role in adaptive immune response to the tumor; (2) antigen presentation, which regulates T-cell-mediated immune response; (3) metabolism, including IDO1, IDO2 and TDO that play an important role in tumor-immune escape 16 , and (4) phagocytosis, which may eliminate the tumor cells in an antibody-dependent manner 9 . We found that, in general, these regulatory genes were expressed more abundantly in the TBME than BC, indicating that the tumor-adjacent brain microenvironment was reprogrammed for immune modulation (Fig.…”

“…While metastasis is the process of dissemination of cancer cells from the primary lesion to distant locations, the tumor microenvironment (TME), which includes the tumor stroma, blood vessels and immune cells, plays an essential role in promoting cancer cell migration and invasion of the basement membrane for the initiation of metastasis, and facilitating the colonization and growth of the cancer cells at the site of metastasis 9 . The human brain is an immunologically privileged organ that provides a “hostile” environment for the seeding and colonization of metastatic tumor cells compared to other organs 9 , 10 . Nevertheless, recent studies have suggested the presence of a brain metastatic niche, or tumor-supporting TME, that sustains the survival of the metastatic cancer cells in patients 11 .…”

“…A recent single-cell RNA-sequencing (scRNA-seq) analysis of metastatic lung adenocarcinoma (LUAD), a main subtype of NSCLC, showed that the cancer cells and cells in the TME indeed undergo extensive molecular and cellular reprogramming to create a pro-tumor and immunosuppressive environment conducive for metastasis 13 . Likewise, a multi-omics study of 15 metastatic cancers has demonstrated that the brain metastatic niches from different cancers are characterized with an immune evasive TME featuring metastasis-associated macrophages (MAMs) and heterogeneous T-cell responses 9 . Furthermore, the brain cells within the metastasis niche may be reprogrammed to facilitate cancer cell proliferation; and the cancer cells, on the other hand, may adopt certain characteristics of the brain cells to survive and flourish in the intracranial environment.…”

Effectiveness of Immune Checkpoint Inhibition vs Chemotherapy in Combination With Radiation Therapy Among Patients With Non–Small Cell Lung Cancer and Brain Metastasis Undergoing Neurosurgical Resection

“… 28 Immune monitoring or evaluation of experimental (biomarker) end points by deploying multiplex approaches before or during treatment might provide insights into the dynamics of immune cells in these patients and potentially lead to discovery of new biomarkers. 22 , 25 , 29 , 30 , 31 …”

Exploring the Impact of TREM2 in Tumor-Associated Macrophages

“…Moreover, a recent study examined brain metastases from different cancer types (melanoma, breast, lung, ovarian, colorectal, and renal cancer) and revealed a cluster of TREM2 + macrophages (APOE, SPP1, C1QA-C, APOC1, FCGR3A) [75], supporting a possible impact of TREM2 in the metastatic process. Finally, an integrated transcriptomic analysis from multiple datasets of human cancers identified TREM2-expressing TAMs in lung, colon, liver, breast, stomach, pancreas, ovaries, skin, kidney, as well as head and neck cancers [73,74,76,77].…”