Table 1

Phenotypic and functional complexity of tumor-immune landscapes revealed by high-dimensional and single-cell analysis technologies

Cancer typeHigh dimensional technologiesKey observationsReferences
Clear cell renal cell carcinomaCyTOF, mIHC
  • Broad expression of PD1 on T cells with heterogeneous expression of TIM3, CTLA4 and 4-1BB.

  • CD38+ CD204+ CD206- TAMs colocalized with CD8+ T cells and is correlated with immunosuppression in tumor tissue.

Chevrier et al, 201837
Hepatocellular carcinomaCyTOF, mIHC
  • Differential enrichment of various immune subsets in the TME vs the non-TME and PBMC.

  • Tregs and exhausted CD8+ T cells were particularly enriched in the TME.

  • TRMs (CD103+ CD45RO+ CD8+) and TEMs (CD45RO+ CCR7- CD8+) that had higher expression of exhaustion markers (PD1, CTLA4 and Lag3) were more abundant in advanced-stage tumors, implicating their roles in tumor progression.

Chew et al, 201738
Hepatocellular carcinomascRNA-Seq, mIHC
  • Differential enrichment of immune subsets such as exhausted CD8+ T cells, MAIT cells and Tregs in tumor vs adjacent normal tissue.

  • Association of LAYN expression with Tregs and exhausted CD8+ T cells.

  • Novel CD8+ FoxP3+ regulatory-like cells were present in the HCC TME.

  • Greater clonal expansion indicating tumor reactivity of CD8+ T cells and Tregs within the TME as compared with non-TME and PBMC.

Zheng et al, 201739
Breast carcinomascRNA-Seq
  • Greater heterogeneity in T cell and myeloid cell types in the TME, with genes related to signaling pathways like inflammation and hypoxia.

  • Phenotypic states of T cells were affected by both TCR stimulation and the signals from the TME.

  • Findings support the continuous T cell activation but not macrophage polarization model in cancer.

Azizi et al, 201840
Basal cell carcinomascATAC-Seq
  • Exhausted CD8+ T cells and T follicular helper cells were expanded post-anti-PD1 immunotherapy.

  • These cells potentially share a common gene regulatory program which drives their development post-immunotherapy.

Satpathy et al, 201942
Triple-negative breast cancerMIBI
  • Tumor tissue architectures are correlated with expression of PD1, PD-L1 and IDO.

  • Compartmentalized tumors, that is, ordered immune structures along with tumor border, is associated with superior survival of the patients.

Keren et al, 201843
Colorectal cancerscRNA-Seq, mIHC
  • Tumor tissue was enriched with T cells with more exhausted, clonally expanded and less mobile phenotypes while the normal tissue and PB was associated with a more naive or recently activated phenotype.

  • CXCL13+ BHLHE40+ IFNG+ Th1-like cells were clonally expanded and enriched in tumors that displayed microsatellite instability, providing a possible explanation for their response to checkpoint blockade therapy.

Zhang et al, 201841
Lung adenocarcinomaCyTOF, scRNA-Seq, mIHC
  • Reduced T effector/Treg ratio and NK cell and CD16+ monocyte numbers in tumor tissue.

  • Reduced CD141+ DCs and increased PPARĪ³hi macrophages in tumor

  • CD141+ DCs were implicated in formation of TLS.

  • Targeting tumor-infiltrating myeloid subsets could potentially enhance T cells response.

Lavin et al, 201744
  • CyTOF, cytometry by time of flight; DC, dendritic cell; HCC, hepatocellular carcinoma; IDO, indoleamine-pyrrole 2,3-dioxygenase; MAIT cells, mucosal-associated invariant T cells; MIBI, multiplexed ion beam imaging; mIHC, multiplex immunohistochemistry; NK, natural killer; PBMC, peripheral blood mononuclear cell; scATAC-Seq, single-cell assay for transposase-accessible chromatin sequencing; TAM, tumor-associated macrophage; TCR, T cell receptor; TLS, tertiary lymphoid structures; TME, tumor microenvironment.