Table 2.
Representative studies of high throughput single-cell sequencing in research of tumor immune microenvironment
| Tumor | Methods | Cases | Samples | Therapy/treatment | Main findings |
|---|---|---|---|---|---|
| NSCLC | scRNA-seq/scTCR-seq | 14 | Tumor/normal/blood | Treatment-naïve | Two pre-exhaustion CD8+ T cells were identified in NSCLC |
| scRNA-seq | 5 | Tumor/normal | Treatment-naïve | By comparing matched normal sites, a tumor environment atlas of NSCLC was constructed | |
| scRNA-seq | 30 | Tumor/normal | Treatment-naïve | PD-1 expressing Trm cells were more proliferative and cytotoxic than PD-1 expression non-Trm cells in NSCLC | |
| scRNA-seq | 44 | Tumor/normal/nLN/mLN/PE/mBrain | Treatment-naïve | In addition to drawing a landscape of LUAD TME, a cancer cell cluster deviated from the normal differential trajectory and was enriched at the metastasis site | |
| scRNA-seq | 42 | Tumor/normal | Treatment-naïve | Several rare cell types in the tumor site, such as follicular dendritic cells and T helper 17 cells, were identified, | |
| scRNA-seq | 30 | Tumor/normal/mLiver/PE/mLN/mBrain | Treatment-naïve/targeted-treatment | scRNA-seq of metastatic lung cancer revealed a rich and dynamic tumor ecosystem | |
| scRNA-seq | 7 | Tumor/blood | Treatment-naïve/chemo-treated | Mapping tumor-infiltrating myeloid cells in patients with NSCLC by scRNA-seq | |
| BC | scRNA-seq/WES/RNA-seq | 11 | Tumor | Treatment-naïve | Highly intratumoral heterogeneity tumor environment was shaped by tumor cells and immune cells in breast cancer |
| scRNA-seq/scTCR-seq | 8 | Tumor/normal/blood/LN | Treatment-naïve | Supported continuous activation model of T cells and disagreed with macrophage polarization model in breast cancer | |
| scRNA-seq/scTCR-seq/RNA-seq | 123 (2 for scRNA-seq) | Tumor | Treatment-naïve | Tissue-resident memory T cells were enriched in breast cancer and expressed high levels of immune molecule and effector proteins | |
| scRNA-seq/scTCR-seq | 14 | Tumor | Treatment-naïve | Drew an atlas of tumor microenvironment of TNBC and defined a novel TCR-expressing macrophage | |
| HCC | scRNA-seq/scTCR-seq | 6 | Tumor/normal/blood | Treatment-naïve | Eleven T cell clusters were defined, and several specific clusters such as exhausted CD8+ T cells were enriched in the HCC tumor site |
| scRNA-seq | 19 | Tumor | Treatment-naïve | Hypoxia-dependent VEGF was associated with tumor diversity and TME polarization. The cytotoxic capacity of T cells was lower in higher heterogeneity HCC | |
| scRNA-seq/scTCR-seq/CyTOF | 13 | Tumor/non-tumor/leading-edge | Treatment-naïve | Defined tumor-associated CD4/CD8 double-positive T cells in HCC and systematically analyzed the function of PD-1+ DPT in HCC | |
| scRNA-seq | 5 | Tumor | Treatment-naïve | Constructed a human liver cancer landscape in single-cell resolution | |
| scRNA-seq/scTCR-seq | 16 | Tumor/normal/blood/ascites/nLN | Treatment-naïve | Drew an immune cell atlas of HCC. A novel DC cluster with high expression of LAMP3 was defined, and it may regulate multiple immune cells | |
| scRNA-seq/RNA-seq | 48 (6 for scRNA-seq) | Tumor/normal/margin tissue | Treatment-naïve | Comprehensively analyzed tumor ILC composition and found that patients with higher IL-33 expression exhibited a higher ILC2/ILC1 ratio, indicating better prognosis | |
| Melanoma | scRNA-seq/WES | 19 | Tumor | Treatment-naïve | Demonstrated the tumor environment ecosystem and how scRNA-seq offers insights into the results |
| scRNA-seq/scTCR-seq | 25 | Tumor | Treatment-naïve | scRNA-seq analysis revealed gradual T cell dysfunction in melanoma and exhausted CD8+ T cells were proliferative and expanded cell cluster | |
| scRNA-seq/scDNA-seq/TCR-seq | 11 | Tumor | Treatment-naïve | Novel CD8+ T cells were observed with predominantly expressing LAG-3, rather than PD-1 or CTLA-4 | |
| CRC | scRNA-seq | 11 | Tumor/normal | Treatment-naïve | Two distinct CAF clusters were identified. Tumor-enriched CAF clusters highly expressed EMT-related genes |
| scRNA-seq/scTCR-seq | 12 | Tumor/normal/blood | Treatment-naïve | Developed STARTRAC indices to analyze the relationship, function, and clonality of 20 identified T cell clusters in CRC | |
| scRNA-seq | 1 | Tumor/normal | Treatment-naïve | Expression clustering identified six gene modules, and functional enrichment was associated with T cells and cancer cells | |
| scRNA-seq/scTCR-seq | 18 | Tumor/normal/blood | Treatment-naïve | Two specific macrophages and cDC clusters, which played a key role of cellular crosstalk in the CRC TME were identified | |
| scRNA-seq | 29 | Tumor/normal | Treatment-naïve | Provided the tumor environment landscape and intercellular communications in CRC | |
| Bladder cancer | scRNA-seq/scTCR-seq | 7 | Tumor/normal | Treatment-naïve | Found multiple tumor-specific CD4 + T cells. Cytotoxic CD4 + T cells in tumor site were highly proliferative and could kill autologous tumors in an MHC class II-dependent manner |
| scRNA-seq | 11 | Tumor/blood | Treatment-naïve | Constructed a cell atlas in bladder cancer and provided deep insights into the tumor microenvironment | |
| ICC | scRNA-seq | 4 | Tumor/adjacent tissue | Treatment-naïve/recurrent | Demonstrated intertumor heterogeneity of human ICC and provided information on intercellular crosstalk between tumor cells and vCAFs |
| Gastric cancer | scRNA-seq | 8 | Tumor/metaplasia/normal/blood | Treatment-naïve | Comparing to normal site, scRNA-seq analysis revealed tumor-enrichment immune cells, transcriptional states, and intercellular interactions in gastric cancer |
| ccRCC | Mass cytometry/RNA-seq | 47 | Tumor/normal | Treatment-naïve/treatment | By profiling 3.5 million single cells, the study developed an in-depth tumor microenvironment atlas of ccRCC and revealed potential biomarkers for therapy strategies |
| Nasopharyngeal | scRNA-seq/scTCR-seq | 3 | Tumor | Treatment-naïve | Provided insights into the tumor microenvironment at single-cell resolution and revealed heterogeneity of immune cells and various functional T cell clusters in NPC |
| Ovarian cancer | scRNA-seq | 9 | Tumor/normal/benign | Treatment-naïve | Identified specific cell clusters enriched in different grades of ovarian cancer |
| Pan-cancer | scRNA-seq/scTCR-seq | 14 | Tumor/normal/blood | Treatment-naïve | Together with published data, demonstrated that non-exhausted T cells from outside of the tumor can replace exhaustion T cells in responsive patients |
| scRNA-seq | 20 | Tumor/normal | Treatment-naïve | Provided an integration immune cell atlas across lung, breast, and ovarian cancers and revealed the complexity of stromal cells in different cancer types | |
| scRNA-seq/RNA-seq/Exome-seq | 48 | Tumor/normal/blood/LN | Treatment-naïve | Drew a pan-cancer myeloid landscape via scRNA-seq. Different sources of LAMP3+ DCs exhibited various transcription expression patterns, and TAMs were also diverse across cancer types |