High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy
Abstract
Simple Summary
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Patient Cohort
4.2. Antibody Staining and Flow Cytometry
4.3. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameters | Characteristics | N (%) |
---|---|---|
Age at start of immunotherapy, years n (%) | Median | 65 |
Range | 24–85 | |
>75 years | 6 (17) | |
Sex, n (%) | Male Female | 19 (54) 16 (46) |
Histology, n (%) | Adenocarcinoma Squamous cell carcinoma mixed | 23 (66) 7 (20) 5 (14) |
Smoking status | Current or former smokers Never smokers | 30 (86) 5 (14) |
PD-L1/CD274 tumor expression, n (%) | <1% ≥1–49% >49 Missing | 11 (31) 9 (26) 14 (40) 1 |
Response, n (%) | Stop after 2 treatment cycles Progressive disease after ≥3 cycles disease stabilization Partial remission | 9 (25.7) 12 (34.3) 7 (20.0) 7 (20.0) |
Immune Cell Subtypes | Clinical Response | Progression | p-Value | AUC | Cut-off Value |
---|---|---|---|---|---|
Leukocytes (cells/μL) | 8597 ± 2262 | 9600 ± 3175 | |||
Neutrophils (cells/μL) | 6214 ± 1948 | 7326 ± 3140 | |||
Monocyte counts (cells/μL) | 626 ± 160 | 672 ± 261 | |||
CD14+CD16+ monocytes (% of monocytes) | 23.6 ± 19.3 | 16.4 ± 11.6 | |||
CD14+HLA-DR++CD16+ monocytes (% of monocytes) | 8.3 ± 3.8 | 7.7 ± 4.3 | |||
Lymphocytes (cells/μL) | 1459 ± 520 | 1413 ± 628 | |||
CD303+ pDC counts (cells/μL) | 10.6 ± 6.2 | 5.9 ± 3.9 | 0.009 | 0.745 | 7.01 |
CD303+ pDC (% of leukocytes) | 0.119 ± 0.054 | 0.070 ± 0.050 | 0.011 | 0.769 | 0.061 |
CD1c+ mDC (cells/μL) | 13.2 ± 8.5 | 9.3 ± 8.6 | |||
CD1c+ mDC (% of leukocytes) | 0.146 ± 0.068 | 0.089 ± 0.064 | 0.018 | 0.755 | 0.104 |
CD141+ mDC (% of leukocytes) | 0.0122 ± 0.009 | 0.006 ± 0.001 | 0.019 | ||
Monocytic CD274 intensity (MFI) | 450 ± 180 | 757 ± 468 | 0.027 | 0.750 | 480 |
CD274 intensity of pDC (MFI) | 398 ± 194 | 609 ± 331 | 0.042 | 0.722 | 440 |
CD274+ pDC (% of pDC) | 12.5 ± 11.0 | 24.5 ± 15.4 | 0.022 | 0.730 | 16.0 |
CD274 intensity of CD1c+ mDC (MFI) | 433 ± 214 | 633 ± 322 | 0.041 | 0.705 | 450 |
CD274+ mDC (% of CD1c+ mDC) | 15.09 ± 13.77 | 26.0 ± 18.11 | 0.062 |
A | Cut-Off Value | n | Kaplan–Meier | Cox Regression | ||||
---|---|---|---|---|---|---|---|---|
% Censored | PFS Time (Months) | Log-Rank Test | HR | 95% CI | p-Value | |||
Blood pDC counts (cells/μL) | ≤7.0 | 18 | 11.1 | 3.65 ± 1.236 | 0.002 | 3.455 | 1.427–8.365 | 0.006 |
>7.0 | 17 | 52.9 | 15.46 ± 2.76 | |||||
Monocytic CD274 expression (MFI) | <480 | 16 | 56.3 | 16.00 ± 2.87 | 0.007 | 3.116 | 1.242–7.814 | 0.015 |
≥480 | 18 | 11.1 | 4.62 ± 1.64 | |||||
CD274 MFI of pDC | ≤440 | 19 | 47.4 | 13.95 ± 2.65 | 0.026 | 2.414 | 1.029–5.660 | 0.043 |
>440 | 14 | 14.3 | 5.23 ± 2.08 | |||||
CD274+ pDC (% of pDC) | ≤16 | 17 | 58.8 | 16.66 ± 2.73 | 0.001 | 4.14 | 1589–10,784 | 0.004 |
>16 | 14 | 7.1 | 3.32 ± 0.96 | |||||
CD274 MFI of CD1c+ mDC | <450 | 15 | 53.3 | 15.01 ± 3.04 | 0.031 | 2.464 | 0.997–6.086 | 0.051 |
≥450 | 18 | 16.7 | 6.57 ± 2.12 | |||||
B | Cut-Point | n | Kaplan–Meier | Cox Regression | ||||
% Censored | OS Time (Months) | Log-RankTest | HR | 95% CI | p-Value | |||
Blood pDC counts (cells/μL) | ≤7.0 | 18 | 11.1 | 5.94 ± 1.27 | 0.002 | 3.548 | 1.477–8.523 | 0.005 |
>7.0 | 17 | 52.9 | 16.8 ± 2.44 | |||||
Monocytic CD274 expression (MFI) | <480 | 16 | 56.3 | 17.06 ± 2.61 | 0.004 | 3.343 | 1.334–8.376 | 0.010 |
≥480 | 18 | 11.1 | 6.83 ± 1.63 | |||||
CD274 MFI of pDC | ≤440 | 19 | 47.4 | 15.21 ± 2.41 | 0.028 | 2.397 | 1.024–5.607 | 0.044 |
>440 | 14 | 14.3 | 7.57 ± 2.04 | |||||
CD274+ pDC (% of pDC) | ≤16 | 17 | 58.8 | 17.78 ± 2.44 | 0.001 | 4.011 | 1.532–10.501 | 0.005 |
>16 | 14 | 7.1 | 6.5 ± 1.54 | |||||
CD274 MFI of CD1c+ mDC | <450 | 15 | 53.3 | 16.33 ± 2.72 | 0.035 | 2.441 | 0.989–6.023 | 0.053 |
≥448 | 18 | 16.7 | 8.61 ± 1.99 |
Correlation of | CC | p-Value |
---|---|---|
Monocytic CD274 Expression with | ||
CD274 expression of pDC | 0.954 | <0.001 |
CD274 expression of CD1c+ mDC | 0.861 | <0.001 |
CD274+ pDC (% of pDC) with | ||
Proportion of pDC (% of leukocytes) | –0.523 | 0.003 |
Proportion of CD1c+ mDC (% of leukocytes) | –0.416 | 0.022 |
Lymphocytes (cells/μL) | –0.632 | <0.001 |
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Riemann, D.; Schütte, W.; Turzer, S.; Seliger, B.; Möller, M. High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy. Cancers 2020, 12, 2966. https://doi.org/10.3390/cancers12102966
Riemann D, Schütte W, Turzer S, Seliger B, Möller M. High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy. Cancers. 2020; 12(10):2966. https://doi.org/10.3390/cancers12102966
Chicago/Turabian StyleRiemann, Dagmar, Wolfgang Schütte, Steffi Turzer, Barbara Seliger, and Miriam Möller. 2020. "High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy" Cancers 12, no. 10: 2966. https://doi.org/10.3390/cancers12102966
APA StyleRiemann, D., Schütte, W., Turzer, S., Seliger, B., & Möller, M. (2020). High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy. Cancers, 12(10), 2966. https://doi.org/10.3390/cancers12102966