Skip to main content

Table 2 Application of scRNA-seq in tumor-associated macrophages (TAMs)

From: Roles of tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for solid cancers

Research Field

Cancer

Findings

References

Identification of different macrophage subsets

Small cell lung cancer

This study identified a profibrotic, immunosuppressive monocytes/macrophage population that is particularly associated with a PLCG2 high small cell lung cancer subpopulation.

[98]

Breast cancer

ScRNA-seq reveals two subsets of APOE+ macrophages: the TREM2+ macrophages and the FOLR2+ macrophages. FOLR2+ macrophages are tissue-resident cells.

[99]

Renal tumor

The study found a novel, tumor-specific sub-population of macrophages and differentially expressed genes (i.e., C1QA-C, APOE, and TREM2).

[100]

Construction of the tumor microenvironment maps

Gallbladder cancer

M2-like macrophages, epithelial cells, and Treg were predominant in ErbB pathway mutation tumors.

[101]

Breast cancer

Most of the non-cancer cells are immune cells, with three distinct clusters of T lymphocytes, B lymphocytes and macrophages. Macrophages have an M2 phenotype that expresses many M2 genes, such as CD163, MS4A6A, and TGFBI, as well as genes known to promote tumor progression and angiogenesis, such as PLAUR13 and IL-8, exhibit immunosuppressive signatures.

[102]

Glioma

Microglia-derived TAMs dominate in newly diagnosed tumors. However, they are overtaken by monocytes-derived TAMs after tumor recurrence, particularly in hypoxic tumor settings.

[103]

Identification of potential prognostic markers

Glioma

Sex-specific gene expression in glioma-activated microglia (e.g., genes encoding MHCII complexes) may be associated with morbidity and outcomes in patients with gliomas.

[104]

Breast cancer

FOLR2+ macrophages positively correlate with better prognosis.

[99]

Renal tumor

TREM2/APOE/C1Q+ macrophages infiltration is a potential prognostic biomarker for clear cell renal carcinoma recurrence.

[100]

Analysis of intercellular interactions in TME

Gallbladder cancer

High levels of midkine, expressed by the ErbB pathway mutation tumor cells, interact with the receptor LRP1 of tumor-infiltrating macrophages and promote immunosuppressive macrophage differentiation. The crosstalk between CXCL10 secreted by macrophage and its receptor CXCR3 on Tregs was induced in gallbladder cancer with ErbB pathway mutations.

[101]

Breast cancer

FOLR2+ macrophages interact with tumor-infiltrating CD8+ T cells.

[99]

Metastatic ovarian cancer

Macrophages in stress-high samples exhibited significantly higher expression of immunosuppressive features (C1QA, C1QB, C1QC, APOE, and TREM2), wherein TREM2 is functionally associated with T cell exhaustion.

[105]

Head and neck tumors

The main contributors of PD-L1 in the TME were dendritic cells and macrophages. PD-1-PD-L1 interactions appeared to be primarily mediated by macrophages. PD-L1+ macrophages spatially associate with CD8+ T cells in the head and neck squamous cell carcinoma microenvironment.

[106]

Gastric cancer

This study uncovered macrophages may contribute to HLA-E-KLRC1/KLRC2 interaction with cytotoxic CD8+ T cells and natural killer cells.

[107]

Colon cancer

In tumors, TAMs and dendritic cells, as the core of the predictive network harbor the most connections with other cell types.

[108]

Explore the mechanisms of drug intervention

Colon cancer

Two distinct TAMs subsets show differential sensitivity to CSF-1R blockade treatment with anti-CSF-1R preferentially depletes macrophage populations with an inflammatory signature but spare macrophage subset that expresses proangiogenic and tumorigenic genes.

[108]

Pan-cancer

Anti-PD-1 therapy decreases the number of Arg-1+ TAMs while increasing Arg-1-TAMs. On a local scale, a new cell subpopulation rich in chemotaxis and interferon response genes is formed.

[109]

Pancreatic cancer

Anti-CD47 treatment led to changes in TME with increased pro-inflammatory macrophages, while reduced anti-inflammatory macrophages.

[110]

Metastatic lung cancer

Macrophages demonstrated an inversion in relative abundance during tumor response and resistance to treatment.

[111]

Explore the mechanisms of drug resistance

Metastatic ovarian cancer

Stress-associated cancer cells strongly associate with a shift toward immunocompromised states within macrophages and CD8+ T cells. This stress-associated state provides cancer cells with adaptation, promoting chemoresistance.

[105]

Pan-cancer

Tumor vessel co-option is a resistance mechanism against anti-angiogenic therapy. Matrix-remodeling macrophages might assist invasive cancer cells to co-opt vessels. An M1-like macrophage subtype may keep vascular cells quiescent.

[112]

Explore the mechanisms of non-drug interventions

Pancreatic cancer

After radiofrequency ablation, the percentage of Mac_s5 lacking mature markers decreased significantly; The proportion of Mac_s1 with anti-inflammatory gene expression profiles was also significantly reduced, and the proportion of Mac_s2 and Mac_s3 cells with anti-tumor functions increased.

[113]

  1. Abbreviations: TAMs Tumor-associated macrophages