Novel tumor-associated macrophage populations and subpopulations by single cell RNA sequencing

Abstract

Tumor-associated macrophages (TAMs) are present in almost all solid tumor tissues. 16They play critical roles in immune regulation, tumor angiogenesis, tumor stem cell activation, tumor invasion and metastasis, and resistance to therapy. However, it is unclear how TAMs perform these functions. With the application of single-cell RNA sequencing (scRNA-seq), it has become possible to identify TAM subpopulations associated with distinct functions. In this review, we discuss four novel TAM subpopulations in distinct solid tumors based on core gene signatures by scRNA-seq, including FCN1+, SPP1+, C1Q+ and CCL18+ TAMs. Functional enrichment and gene expression in scRNA-seq data from different solid tumor tissues found that FCN1+ TAMs may induce inflammation; SPP1+ TAMs are potentially involved in metastasis, angiogenesis, and cancer cell stem cell activation, whereas C1Q+ TAMs participate in immune regulation and suppression; And CCL18+ cells are terminal immunosuppressive macrophages that not only have a stronger immunosuppressive function but also enhance tumor metastasis. SPP1+ and C1Q+ TAM subpopulations can be further divided into distinct populations with different functions. Meanwhile, we will also present emerging evidence highlighting the separating macrophage subpopulations associated with distinct functions. However, there exist the potential disconnects between cell types and subpopulations identified by scRNA-seq and their actual function.

An update to experimental and clinical aspects of tumor-associated macrophages in cancer development: hopes and pitfalls

“…Current scRNA-seq investigations predominantly focus on some solid tumors like glioma, breast cancer, and lung cancer [ 17 – 19 ]. In various solid tumor tissues, functional enrichment analysis and gene expression profiling in scRNA-seq data delineate distinct roles for different tumor-associated macrophages (TAMs): FCN1 + TAMs show a proinflammatory influence, SPP1 + TAMs are implicated in metastasis, angiogenesis, and cancer stem cell activation, C1Q + TAMs play a role in immune regulation and suppression, and CCL18 + cells represent terminal immunosuppressive macrophages with potent immunosuppressive abilities and the capacity to promote tumor metastasis[ 20 ]. By studying TAM heterogeneity, scRNA-seq explains the correlation between tissue-specific macrophage subtypes and tumor progression within the tumor microenvironment, conveying valuable insights for patient prognosis.…”