Single-cell spatial immune landscapes of primary and metastatic brain tumours

Abstract

Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell–cell relationships within the tumour microenvironment1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues3. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.

The Glioma Immune Landscape: A Double-Edged Sword for Treatment Regimens

“…In this regard, Shaim et al reported that targeting the αv integrin/TGF-β axis helps enhance NK cell function against GBM stem cells in vitro [ 110 ]. Recently, Karimi et al found that a subset of neutrophil-like macrophages positive for myeloperoxidase (MPO) could be beneficial for the survival of GBM patients [ 223 ]. Thus, inhibiting the αv integrin/TGF-β axis or enhancing the population of MPO+ macrophages, along with employing known immunotherapeutic techniques, needs to be tested as an alternative glioma therapy.…”

Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts

“…Lastly, we did not observe major differences between PDOXs derived from treatment-naïve and recurrent GBMs. In summary, mouse-derived TME in PDOXs is composed of cellular types relevant to human GBM 4 .…”

“…The brain TME includes endothelial cells, pericytes, astrocytes, neurons, oligodendrocytes and immune cells. Although GBMs are known as 'cold tumors' with very little lymphocytic infiltration 3 , the GBM TME contains up to 40% of myeloid cells, which, as a whole, are referred to as tumorassociated macrophages (TAMs) and are known to create a supportive environment facilitating tumor proliferation, survival and migration 4,5 . TAMs are mainly constituted by brain resident parenchymal microglia (Mg), peripheral monocytes (Mo) and perivascular macrophages, known as border-associated macrophages (BAMs) [6][7][8] .…”

A single-cell transcriptomic atlas characterizes molecular features in ureteritis/cystitis induced by immune checkpoint inhibitors

“…The cellular and molecular mechanisms of ICI-induced ureteritis/cystitis are not well understood, which precludes their optimal clinical management. Single-cell RNA sequencing (scRNA-seq) offers an opportunity for identifying disease-associated cell subsets and molecular features in human tissues at high resolution and in an unbiased fashion (13). Here, we reported two cases of immune-related ureteritis/cystitis, which were induced by an anti-PD-1 monoclonal antibody (mAb).…”