Advancing Understanding of Non-Small Cell Lung Cancer with Multiplexed Antibody-Based Spatial Imaging Technologies
Abstract
:Simple Summary
Abstract
1. Introduction
2. Literature Review
2.1. Prediction of Recurrence and Survival Following Curative-Intent Resection
2.2. Prediction of Benefit from Immunotherapy
2.3. Study of CD8+ T-Cells in Early-Stage Resected NSCLC
2.4. Other Multiplexed Antibody-Based Studies
3. Discussion
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Widely Expressed Cell Surface Markers | ||||
---|---|---|---|---|
FAS | MHC-I | |||
T-cell markers | ||||
CD3 | CD4 | CD8 | CD45RA | CD45RO |
CD103 | CD127 | FoxP3 | LAG-3 | |
Co-inhibitory molecules | ||||
B7-H3 | B7-H4 | CTLA-4 | IDO-1 | PD-1 |
PD-L1 | PD-L2 | TIM-3 | VISTA | |
Co-stimulatory molecules | ||||
CD27 | CD28 | CD40 | CD80 | CD86 |
ICOS | OX40 | |||
M2-like macrophage markers | ||||
CD163 | CD168 | |||
Secreted pro-inflammatory molecules | ||||
IFN-γ | TNF-α | GZMB | ||
Secreted tolerance-promoting molecules | ||||
IL-6 | IL-10 | TGF-β | ARG-1 | |
Other immune cell markers | ||||
CD11b (myeloid cells; NK cells) | CD11c (DCs; NK cells; activated T- or B-cells) | |||
CD25 (DCs) | CD45 (pan-leucocyte) | CD56 (NK cells) | ||
CD66b (TANs) | CD68 (pan-macrophage) | |||
Other cell surface markers | ||||
CD34 (CAFs; endothelial cells) | CD44 (CSCs; CAFs) | |||
Cytokeratins (tumour cells) | Ki-67 (proliferating cells) |
Reference; Multiplexing Method | Setting | Finding | Outcome Predicted | Reported Measure of Predictive Value |
---|---|---|---|---|
Barua et al. [52]; TSA | Post curative-intent resection | Tumour cell/T-reg interactions | Inferior OS | Greater AUC of cross-G function: HR 1.52; 95%CI 1.11–2.07, p = 0.009 |
CD8+T/T-reg interactions | Superior OS | Greater AUC of cross-G function: HR 0.96; 95%CI 0.92–0.99, p = 0.042 | ||
Backman et al. [58]; mIF | Post curative-intent resection | Greater CD8+ effector/ tumour cell proximity | Superior OS | Stepwise Cox regression: HR 0.29, p <0.05 |
Greater M2 macrophage/ M1 macrophage proximity | Inferior OS | Stepwise Cox regression: HR 2.33, p <0.05 | ||
Greater B-cell/ CD4+ T-reg proximity | Superior OS | Stepwise Cox regression: HR 0.59, p <0.05 | ||
Greater CD8+ T-reg/ B-cell proximity | Superior OS | Stepwise Cox regression: HR 0.46, p <0.01 | ||
Sorin et al. [59]; IMC | Adenocarcinoma (mixed-stage) | Frequent ‘B-cell-enriched’ CNs | Superior OS | Log-rank test: p = 0.001 |
Frequent ‘lymphoid enriched’ CNs | Superior OS | Log-rank test: p = 0.039 | ||
Frequent ‘pan-immune hotspot 1’ CNs | Superior OS | Log-rank test: p = 0.026 | ||
Frequent ‘undefined’ CNs | Inferior OS | Log-rank test: p = 0.006 | ||
Adenocarcinoma (stage I) | Deep learning signature lineage marker model | Recurrence | Prediction score: 95.9% (vs 80.55% with clinical variables), p = 0.0343. Validation cohort: Accuracy 94.2% (vs 75% baseline prediction score). | |
Zugazagoitia et al. [61]; DSP | ICI-treated (stage III-IV) | Frequent CD56+ cells in the leucocyte compartment | Superior PFS | Log-rank test: HR 0.24, p = 0.006 |
Superior OS | Log-rank test: HR 0.26, p = 0.014 | |||
Frequent CD4+ cells in the leucocyte compartment | Superior PFS | Log-rank test: HR 0.31, p = 0.006 | ||
Superior OS | Log-rank test: HR 0.23, p = 0.0.007 | |||
Moutafi et al. [63]; DSP | ICI-treated (advanced-stage) | Frequent CD66b+ cells in the leucocyte compartment | Inferior OS | Log-rank test: HR 1.31, p = 0.016 |
Moutafi et al. [64]; DSP | ICI-treated (advanced-stage) | Frequent CD44+ cells in the tumour compartment | Superior PFS | Discovery cohort: log-rank test HR 0.68, p = 0.043 Validation cohort: log-rank test: HR 0.62, p = 0.03 |
Song et al. [66]; DSP | ICI bispecific Ab-treated (advanced-stage); validation set was ICI mAb-treated | Stromal signature | Treatment response | Training set: AUROC 0.838 Validation set: AUROC 0.776 |
Superior PFS | Log-rank test: HR 2.90, p = 0.013 in validation set | |||
Superior OS | Validation set: log-rank test HR 3.44, p = 0.04 | |||
Tumour signature | Treatment response | Training set: AUROC 0.786 | ||
Gerdtsson et al. [67]; DSP | Post curative-intent resection | High B7-H3 expression | Superior OS | Log-rank test: HR 0.60, p = 0.008 |
Sanmamed et al. [71]; IMC, mIF | Post curative-intent resection | Low proportion of CD8+ T-cells with ‘Ebo’ phenotype | Durable clinical benefit | Student’s t-test: p < 0.001 |
ICI-treated (advanced-stage) | Low proportion of CD8+ T-cells with ‘Ebo’ phenotype | Superior OS | Log-rank test: HR 2.66, 95%CI 1.17–6.01, p = 0.03 | |
Yang et al. [73]; mIF | Post curative-intent resection | Low density of ‘pre-dysfunctional’ CD8+ T-cells in tumour centre | Superior RFS | Log-rank test: HR 0.55, 95%CI 0.34–0.89; p = 0.014 |
High density of ‘dysfunctional’ CD8+ T-cells in invasive margin | Inferior RFS | Log-rank test: HR 2.49, 95%CI 1.60–4.13; p = 0.012 | ||
Shorter mNND between CD8+ T-cells and T-regs in invasive margin | Inferior RFS | Log-rank test: HR 1.72, 95%CI 1.26–2.92; p = 0.024 | ||
Shorter mNND between CD8+ T-cells and CAFs in invasive margin | Inferior RFS | Log-rank test: HR 1.57, 95%CI 1.11–2.43; p = 0.024 | ||
Parra et al. [78]; mIF | Adenocarcinoma post curative-intent resection | Greater CD66b+ cell/ tumour cell proximity | Superior RFS | Log-rank test: p = 0.028 |
Greater CD3+CD8+ cell/ tumour cell proximity | Superior RFS | Log-rank test: p = 0.041 | ||
Greater CD68+ cell/ tumour cell proximity | Superior RFS | Log-rank test: p = 0.021 | ||
Greater CD3+B7-H3+ cell/ tumour cell proximity | Inferior RFS | Log-rank test: p = 0.022 | ||
Squamous cell carcinoma post curative-intent resection | Greater CD3+PD-L1+ cell/ tumour cell proximity | Inferior RFS | Log-rank test: p = 0.012 | |
Greater CD3+ICOS+ T-cell/ tumour cell proximity | Superior RFS | Log-rank test: p = 0.009 |
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Gray, S.; Ottensmeier, C.H. Advancing Understanding of Non-Small Cell Lung Cancer with Multiplexed Antibody-Based Spatial Imaging Technologies. Cancers 2023, 15, 4797. https://doi.org/10.3390/cancers15194797
Gray S, Ottensmeier CH. Advancing Understanding of Non-Small Cell Lung Cancer with Multiplexed Antibody-Based Spatial Imaging Technologies. Cancers. 2023; 15(19):4797. https://doi.org/10.3390/cancers15194797
Chicago/Turabian StyleGray, Simon, and Christian H. Ottensmeier. 2023. "Advancing Understanding of Non-Small Cell Lung Cancer with Multiplexed Antibody-Based Spatial Imaging Technologies" Cancers 15, no. 19: 4797. https://doi.org/10.3390/cancers15194797