Table 3.
Summary table of multiplex imaging studies that describe clinical outcomes, treatment responses, biomarkers, and tumor classification and grading.
| Category | Method | Ref | Year | Cancer Type | Described Observations |
|---|---|---|---|---|---|
|
Clinical
Outcome |
Pheno- Imager |
[41] | 2018 | Lung cancer |
Tumor–T cell interactions in tumor core and CD8+ T cell: Treg cell ratios were associated with overall survival in NSCLC |
| Pheno- Imager |
[45] | 2021 | Ovarian cancer |
High ratios of CD8:FOXP3 and CD8: PD-L1 T cells ratios were associated with favorable overall survival in high-grade serous OC | |
| Pheno- Imager |
[34] | 2018 | Esophageal cancer | High-notch intracellular domain-expressing ESCC tumors have a decreased overall survival rate | |
| Pheno- Imager |
[46] | 2017 | Renal cell carcinoma |
PD-1+LAG3+CD8+ T cells were associated with poorer 36 month overall survival and higher relapse risk | |
| Pheno- Imager |
[47] | 2015 | Prostate cancer |
Lowest quartile nuclear SBP1 expression levels were associated with a higher recurrence risk after radical prostatectomy | |
| Pheno- Imager |
[48] | 2022 | Ovarian cancer |
Increased PD-L1 macrophages, ICOS+ Th > Treg numbers post-therapy, and decreased proximity ICOS+ Th to Treg cells in high-grade serous OC | |
| Pheno- Cycler |
[49] | 2020 | Colorectal cancer |
Specific cellular neighborhoods are associated with overall survival | |
| MIBI-TOF | [21] | 2018 | Breast cancer |
Compartmentalized tumors are associated with increased survival in TNBC | |
| MIBI-TOF | [35] | 2022 | Breast cancer |
Progressors from DCIS to IBC had a thicker and continuous MEC layer | |
| IMC | [22] | 2020 | Breast cancer |
Single-cell pathology grouping improved the prediction of overall survival in TNBC | |
| IMC | [25] | 2021 | Bladder cancer |
Stem-like cell cancer cluster (ALDH+PD-L1+ER-β−) is associated with poor prognosis in MIBC | |
| IMC | [50] | 2022 | Breast cancer |
Structures containing Tregs and exhausted T cells and structures enriched in granulocytes or APC are correlated with poor prognosis in ER−, but not ER+ breast cancer tumors | |
| IMC | [51] | 2021 | Ovarian cancer |
LTS showed increased number of granzyme B+ CTLs and CD45RO+CD4+ T cells, and a reduction in tumor cells and endothelial cells in high–serous OC. Granzyme B+ CD8+ T cells and CD45RO CD4+ interactions were correlated with overall survival | |
| IMC | [52] | 2019 | Gastric cancer |
Responding mFOLFOX-treated tumors showed higher platinum levels compared to non-responders | |
| IMC | [53] | 2021 | Lung cancer |
Abundant Ebo CD8+ TILs are correlated with poor overall survival in NSCLC | |
| MALDI- MSI |
[54] | 2019 | Breast cancer |
Identified nine proteins associated with EGFR related to progression in TNBC | |
| MALDI- MSI |
[55] | 2021 | Colorectal cancer |
Different N-glycosylation patterns in TME to distinguish short- and long-term survivors | |
| MALDI- MSI |
[56] | 2016 | Ovarian cancer |
Different N-glycosylation patterns in TME to distinguish short- and long-term survivors | |
| DSP | [57] | 2020 | Breast cancer |
High CD4 and ICOS expression in stroma and HLA-DR expression in stroma or epithelial compartment were associated with long-term disease-free survival in TNBC | |
| DSP | [58] | 2019 | Lung cancer |
PD-L1 expression in the macrophage compartment was associated with progression-free survival and overall survival in NSCLC | |
| DSP | [59] | 2020 | Lung cancer |
High CD4 and CD56 expression in the immune cell compartment was associated with overall survival, progression-free survival, and durable benefit in NSCLC | |
| DSP | [60] | 2020 | B-cell lymphoma |
High LAG3 expression was associated with poorer progression-free survival and overall survival | |
| DSP | [61] | 2020 | Lung cancer |
Expression of CD3, ICOS, and CD34 in the tumor compartment was associated with improved overall survival in NSCLC | |
| DSP | [62] | 2018 | Melanoma | Low CD3, B2M, and PD-L1 and low IFNγ signature were associated with relapse after adjuvant or neoadjuvant ipilimumab and nivolumab | |
|
Treatment
Response Human |
Pheno- Imager |
[63] | 2021 | Head and neck SCC | CD3+ T cells and CD8+ T cells are increased post-treatment with cetuximab in responders, compared to pre-treatment |
| Pheno- Imager |
[64] | 2017 | Rectal cancer |
Lower CD4: PD-L1, CD8: PD-L1, FOXP3: PD-L1 ratios in total regression compared to residual disease | |
| IMC, MALDI -MSI |
[65] | 2022 | Pancreatic cancer | Gemcitabine metabolites induce γH2AX in KI67+ Phosphorylated-ERK+ and Phosphorylated-S6+ areas in pancreatic ductal adenocarcinoma | |
| IMC | [66] | 2019 | Breast cancer (HER2+) | Elevated ECD/ICD ratio in cytokeratin positive compartment had a lower number of 5-year reoccurrence after trastuzumab | |
| IMC | [67] | 2021 | Rectal cancer |
Reduced Treg cells and TAMs, higher CTL levels were associated with complete response | |
| IMC | [68] | 2021 | Gastro-esophageal | Comparing immune cell composition changes in ramucirumab/paclitaxel-responding patients with or without ICPI administration in gastro-esophageal adenocarcinoma | |
| DSP | [69] | 2021 | Hairy cell leukemia |
Changes in CD8 expression and tumor burden are associated with a durable response to cladribine | |
| DSP | [58] | 2019 | Lung cancer |
PD-L1 expression in the macrophage compartment was associated with immune therapy response in NSCLC | |
| DSP | [70] | 2021 | Head and neck SCC | Immune cell number and CD4, CD68, CD45, CD44, and CD66b were correlated with progressive disease during ICPI treatment | |
| DSP | [71] | 2018 | Melanoma | CD45RO, B2M, CD3, CD8, CD19, CD20, and Ki67 in the immune cell compartment were associated with ICPI response | |
|
Treatment
Response Mice |
Pheno- Imager |
[72] | 2022 | HPV16+ solid tumors | Total macrophages, activated CTL, and number of activated T cells are higher in responders compared to non-responders to HPV16+ vaccine (ISA101) with nivolumab |
| Pheno- Cycler |
[42] | 2022 | Breast cancer |
CD4+ and CD8+ T cell infiltration and interaction increased upon cPLA2 inhibitor treatment | |
| IMC | [73] | 2020 | Biliary tract cancer | Elevated CD8+ T cell numbers in small anti-PD-1 sensitive tumors | |
| IMC | [74] | 2021 | Lung cancer |
Change in immune infiltrate upon KRAS inhibition in NSCLC | |
| IMC | [75] | 2021 | Breast cancer |
ITT and IPT anti-CD40/PD-L1 NDES treatment increased immune subsets and anti-tumor responses in TNBC | |
|
Tumor
Classification & Grading |
Pheno- Imager |
[34] | 2018 | Esophageal cancer | Higher notch intracellular domain expression is correlated with higher tumor stage and grade in ESCC |
| MALDI- MSI |
[76] | 2022 | Lung cancer |
Classifies SCC or AD (NSCLC) based on glutamine or taurine in the TME | |
| MALDI- MSI |
[77] | 2019 | Lung cancer |
Spatial distribution of CK5/6, HSP27, and CK15 to classify SCC or AD (NSCLC) | |
| MALDI- MSI |
[78] | 2010 | Breast cancer |
Identification of cysteine-rich protein 1 in HER2+ breast cancer | |
| MALDI- MSI |
[79] | 2020 | NSCLC | Elevated levels of collagenase type III can discriminate low-grade adenocarcinoma from healthy lung tissue | |
|
Biomarker
Discovery |
IMC | [80] | 2021 | Melanoma | B2M expression in tumor and stroma compartment is correlated with longer overall survival to anti-PD-1 therapy |
| MALDI- MSI |
[81] | 2020 | Lung cancer |
Identification of neutrophil defensins in ICPI-responsive NSCLC patients | |
| MALDI- MSI |
[54] | 2019 | Breast cancer |
Identified nine proteins associated with EGFR related to progression in TNBC |
Abbreviations: AD: Adenocarcinoma, ALDH: aldehyde dehydrogenase, B2M: beta-2 microglobulin, CD3: cluster of differentiation 3, CD4: cluster of differentiation 4, CD8: cluster of differentiation 8, CD19: cluster of differentiation 19, CD20: cluster of differentiation 20, CD34: cluster of differentiation 34, CD40: cluster of differentiation 40, CD44: cluster of differentiation 44, CD45: cluster of differentiation 45, CD56: cluster of differentiation 56, CD66b: cluster of differentiation 66b, CD68: Cluster of Differentiation 68, CK5/6: Cytokeratin 5/6, CK15: Cytokeratin 15, cPLA2: cytosolic phospholipase A2, CTL: cytotoxic T cells, DCIS: ductal carcinoma in situ, DSP: digital spatial analysis, Ebo: burned-out effector, ECD: extracellular domain, EGFR: epidermal growth factor receptor, ER: estrogen receptor, ER-β: estrogen receptor beta, ERK: extracellular signal-regulated kinase, ESCC: esophageal squamous cell carcinoma, FOXP3: forkhead box P3, γH2AX: gamma h2a histone family member X, HER2: human epidermal growth factor receptor 2, HLA-DR: human leukocyte antigen—DR isotype, HPV16: human papilloma virus 16, HSP27: heath shock protein 27, ICD: intracellular domain, ICPI: immune checkpoint inhibition, ICOS: inducible T cell costimulation, IBC: invasive breast cancer, IFNγ: interferon gamma, IMC: imaging mass cytometry, IPT: intraperitoneal treatment, ITT: intratumoral treatment, KRAS: Kirsten rat sarcoma viral oncogene homolog, LAG3: lymphocyte activation gene 3, LTS: long-term survivors, MALDI-MSI: matrix-assisted laser desorption ionization mass spectrometry imaging, MEC: myoepithelial E-cadherin, mFOLFOX: modified folinic acid, fluorouracil, and oxaliplatin, MIBC: muscle invasive bladder cancer, MIBI-TOF: multiplexed ion beam imaging by time-of-flight, NDES: nanofluidic drug-eluting seed, NSCLC: non-small cell lung cancer, OC: ovarian carcinoma, PD-1: programmed cell death protein 1, PD-L1: programmed death-ligand 1, SBP1: selenium binding protein 1, SCC: squamous cell carcinoma, TAM: tumor-associated macrophages, TIL: tumor-infiltrating lymphocyte, TME: tumor microenvironment, TNBC: triple-negative breast cancer, Treg: regulatory T cell.