Table 2.
Summary table of multiplex imaging studies that describe tumor microenvironment heterogeneity, specific cell types, novel immune cell subsets, cellular interactions, or (disease) comparisons.
| Category | Method | Ref | Year | Cancer Type | Described Observations |
|---|---|---|---|---|---|
|
TME
Heterogeneity |
Pheno- Imager |
[19] | 2020 | Breast and lung cancer |
Different (immune) cell compositions within the TME |
| MIBI-TOF | [20] | 2019 | Breast cancer |
Immune cell subset balances and compartmentalization within TNBC TME | |
| MIBI-TOF | [21] | 2018 | Breast cancer |
Different immune cell compositions and immune cell subset balance within the TNBC TME | |
| IMC | [22] | 2020 | Breast cancer |
Various (immune) cell compositions within the TNBC TME | |
| IMC | [23] | 2021 | Lung cancer |
Various (immune) cell compositions within the NSCLC (SCC) TME | |
| IMC | [24] | 2021 | OSCC | Various (immune) cell compositions within the TME | |
| IMC | [25] | 2021 | Bladder cancer |
Different immune cell compositions within the TME | |
| DSP | [26] | 2019 | Prostate cancer |
Different (immune) cell compositions and signaling pathways within the TME of lytic and blastic bone metastasis | |
| DSP | [27] | 2021 | Prostate cancer |
Inter- and intra-tumoral differences in (immune) cell compositions in metastatic prostate cancer | |
|
Specific
Cell Types |
Pheno- Imager |
[9] | 2019 | Colorectal cancer |
FAP-expressing CAFs in the invasive tumor front in stroma-high tumors |
| Pheno- Imager |
[28] | 2021 | Melanoma | Enrichment of innate immune cells, specific DC subset and STAT3 expression Stage IV with leptomeningeal disease | |
| Pheno- Imager |
[29] | 2020 | Colorectal cancer |
TAMs subsets in stromal and epithelial compartments | |
| MIBI-TOF | [17] | 2020 | cSCC | Specific keratinocyte population within the TME | |
| IMC | [30] | 2022 | Lung cancer |
Enriched PD-L1+CD8+ T cell subset in NSCLC | |
| IMC | [31] | 2021 | Breast cancer |
High p-eIF4E expression in tumor cells and change immune cell composition | |
| IMC | [32] | 2021 | Colorectal cancer |
Elevated proliferating and cytotoxic CD8+ T cell subsets in hypermutated CRC | |
|
(Disease)
Comparisons |
Pheno- Imager |
[33] | 2017 | Prostate cancer | P300 increase and SIRT2 decrease when comparing BPH, prostate cancer to metastatic disease |
| Pheno- Imager |
[34] | 2018 | Esophageal cancer | High Notch Intracellular Domain expression in ESCC compared to benign or reactive epithelium | |
| MIBI-TOF | [35] | 2022 | Breast cancer |
Comparing fibroblast composition in healthy breast tissue, DCIS, and IBC. | |
| IMC | [31] | 2021 | Breast cancer |
Comparing Immune cell composition before, during and after pregnancy | |
| IMC | [32] | 2021 | Colorectal cancer |
Comparing Immune cell composition in DB-CRC and nDB-CRC | |
| IMC | [36] | 2018 | Prostate cancer |
Comparing bone marrow, prostate, and metastatic tissue | |
| DSP | [26] | 2019 | Prostate cancer |
Different (immune) cell compositions and signaling pathways when comparing the TME of lytic and blastic bone metastasis | |
| DSP | [37] | 2020 | Endocrine tumors | Comparing the TME of neuroendocrine tumors and neuroendocrine carcinomas | |
| DSP | [38] | 2021 | Glioblastoma | Comparing immune-oncology proteins in methylated and unmethylated isocitrate dehydrogenase wild-type glioblastoma | |
| DSP | [39] | 2021 | Breast cancer | Comparing immune cell profiles in luminal and basal-like breast cancer | |
| DSP | [40] | 2021 | Colorectal cancer | Comparing the TME after neoadjuvant chemotherapy alone or in combination with ICPI in CRC patients | |
|
Cellular
Interactions |
Pheno- Imager |
[41] | 2018 | Lung cancer | Tumor–T cell interactions in tumor core and CD8+ T cell–Treg cells associated with overall survival in NSCLC |
| Pheno- Cycler |
[42] | 2022 | Breast cancer | Increased interaction between CD4+ and CD8+ T cells after cPLA2 treatment in mice | |
|
Novel
Immune |
IMC | [23] | 2021 | Lung cancer | Identification of CD3−CD4+FOXP3+CD25−CD127−TNFα+IFNγ−TdT+ cells in NSCLC (SCC) |
| Subtypes | IMC | [43] | 2020 | Hodgkin lymphoma | CD4+LAG3+ T cells in MHC-II negative classic Hodgkin Lymphoma |
| IMC | [44] | 2019 | Colon cancer | CD4+EpCAM+PD-L1+ T cells with upregulated p38-MAPK-MAPKAPK2 pathway |
Abbreviations: BPH: benign prostatic hyperplasia, CD3: cluster of differentiation 3, CD4: cluster of differentiation 4, CD8: cluster of ddifferentiation 8, CD25: cluster of differentiation 25, CD127: cluster of differentiation 127, CAF: cancer-associated fibroblast, cPLA2: cytosolic phospholipase A2, CRC: colorectal cancer, cSCC: cutaneous squamous cell carcinoma, DB: durable benefit, DC: dendritic cell, DCIS: ductal carcinoma in situ, DSP: digital spatial analysis, EpCAM: epithelial cell adhesion molecule, ESCC: esophageal squamous cell carcinoma, FAP: fibroblast activation protein, FOXP3: forkhead box P3, ICPI: immune checkpoint inhibition, IBC: invasive breast cancer, IFNγ: interferon gamma, IMC: imaging mass cytometry, LAG3: lymphocyte activation gene 3, MAPK: mitogen-activated protein kinase, MAPKAPK2: mitogen-activated protein kinase-activated protein kinase 2, MHC-II: major histocompatibility complex II, MIBI-TOF: multiplexed ion beam imaging by time-of-flight, nDB: non-durable benefit, NSCLC: non-small cell lung cancer, OSCC: oral squamous cell carcinoma, PD-L1: programmed death-ligand 1, p-eIF4E: phospho-eukaryotic translation initiation factor 4E, SCC: squamous cell carcinoma, SIRT2: sirtuin 2, STAT3: signal transducer and activator of transcription 3, TAM: tumor-associated macrophages, TdT: terminal deoxynucleotidyl transferase, TME: tumor microenvironment, TNBC: triple-negative breast cancer, TNFα: tumor necrosis factor alpha, Treg: regulatory T cell.