ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Blood Collection
2.2. Lymphocyte Isolation and Flow Cytometry Analysis
2.3. Isolation and Detection of CTCs
2.4. Statisical Analysis
3. Results
3.1. PD-1-Expressing CD8+ and CD4+ T-Cells in Peripheral Blood of SCLC Patients
3.2. PD-1 Expression Levels in SCLC Patients
3.3. PD-L1-Expressing CTCs and their Correlation with PD-1-Expressing T-Cells
3.4. Correlation of Circulated T-Cells and CTCs with Clinical Outcome
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Sub-Categories | Values |
---|---|---|
Median age | 70 years (range 44–84 years) | |
Gender | Male | 34 (79%) |
Female | 9 (21%) | |
Stage | Limited | 6 (14%) |
Extensive | 37 (86%) | |
Metastasis | Brain | 11 (25%) |
Lung | 13 (30%) | |
Liver | 15 (35%) | |
Bones | 8 (17%) | |
Adrenal gland | 6 (14%) | |
LNs | 7 (16%) | |
Pleural | 14 (33%) | |
other | 4 (9%) | |
Best Response | PR | 26 (60%) |
SD | 1 (2%) | |
Mixed | 2 (5%) | |
Unknown | 14 (33%) | |
Smoking Status | Never | 1 (2%) |
Former | 10 (23%) | |
Curent | 28 (65%) | |
Unknown | 4 (9%) | |
<40 pack year | 8 (19%) | |
40–80 pack year | 13 (31%) | |
>80 pack year | 15 (36%) | |
Unknown | 6 (14%) |
PD-1+ CD3+CD8+ T-Cells | PD-1+ CD3+CD4+ T-Cells | ||||||
---|---|---|---|---|---|---|---|
CTCs | Total | Teff | Tem | Total | Teff | Tem | |
CK+CD45- | Spewrman r | 0.351 | −0.94 | 0.011 | 0.010 | −0.137 | −0.188 |
p-value | 0.038 | 0.611 | 0.952 | 0.957 | 0.485 | 0.336 | |
95% CI | 0.010 to 0.619 | −0.443 to 0.278 | −0.354 to 0.373 | −0.374 to 0.392 | −0.494 to 0.259 | −0.533 to 0.209 | |
CK+CD45-PD-L1- | Spewrman r | −0.064 | −0.165 | −0.72 | −0.059 | −0.198 | −0.276 |
p-value | 0.713 | 0.374 | 0.697 | 0.765 | 0.310 | 0.154 | |
95% CI | −0.398 to 0.284 | −0.499 to 0.211 | −0.425 to 0.299 | −0.433 to 0.330 | −0.540 to 0.199 | −0.596 to 0.119 | |
CK+CD45-PD-L1+ | Spewrman r | 0.342 | −0.132 | −0.65 | 0.064 | −0.132 | −0.119 |
p-value | 0.044 | 0.477 | 0.727 | 0.744 | 0.501 | 0.544 | |
95% CI | −0.000 to 0.612 | −0.473 to 0.243 | −0.419 to 0.306 | −0.326 to 0.436 | −0.490 to 0.264 | −0.480 to 0.276 |
Progresion Free Survival | Overall Survival | |||||||
---|---|---|---|---|---|---|---|---|
T-Cell Populations | ROC Cut Off | Median (Days) | 95% HR CI | p Value | Median (Days) | 95% CI | p Value | |
CD3+CD8+ | 24 | High | 171 | 0.1988 to 1.283 | 0.150 | 271 | 0.1498 to 1.317 | 0.143 |
Low | 153 | 198 | ||||||
CD3+CD8+PD-1 | 22 | High | 172 | 0.1731 to 0.9486 | 0.037 | 394 | 0.1830 to 1.054 | 0.065 |
Low | 153 | 217 | ||||||
CD8+ Teff | 25 | High | 180 | 0.1402 to 0.8555 | 0.021 | 261 | 0.1826 to 1.273 | 0.140 |
Low | 158 | 232 | ||||||
CD8+ Teff PD-1 | 12.7 | High | 167 | 0.1562 to 1.450 | 0.191 | 289 | 0.03718 to 0.6173 | 0.008 |
Low | 149 | 190 | ||||||
CD8+ Tem | 33.6 | High | 164 | 0.8099 to 3.692 | 0.157 | 232 | 0.7701 to 5.062 | 0.156 |
Low | 167 | 394 | ||||||
CD8+ Tem PD-1 | 38 | High | 172 | 0.4013 to 2.091 | 0.835 | 394 | 0.2135 to 1.424 | 0.218 |
Low | 164 | 260 | ||||||
CD3+CD4+ | 41 | High | 158 | 0.4671 to 2.096 | 0.977 | 385 | 0.2410 to 1.380 | 0.216 |
Low | 165 | 246 | ||||||
CD3+CD4+PD-1 | 7.5 | High | 158 | 0.3293 to 1.667 | 0.468 | 289 | 0.2277 to 1.453 | 0.242 |
Low | 164 | 232 | ||||||
CD4+ Teff | 10.7 | High | 157 | 0.4969 to 3.160 | 0.632 | 261 | 0.2563 to 1.668 | 0.374 |
Low | 164 | 232 | ||||||
CD4+ Teff PD-1 | 18 | High | 163 | 0.6510 to 3.038 | 0.385 | 232 | 0.6423 to 3.869 | 0.320 |
Low | 167 | 271 | ||||||
CD4+ Tem | 33.2 | High | 167 | 0.2170 to 1.573 | 0.287 | 232 | 0.4638 to 3.653 | 0.616 |
Low | 153 | 337 | ||||||
CD4+ Tem PD-1 | 7.7 | High | 158 | 0.5744 to 2.720 | 0.573 | 232 | 0.5109 to 3.050 | 0.626 |
Low | 186 | 265 |
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Xagara, A.; Roumeliotou, A.; Kokkalis, A.; Tsapakidis, K.; Papakonstantinou, D.; Papadopoulos, V.; Samaras, I.; Chantzara, E.; Kallergi, G.; Kotsakis, A. ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment. Biomedicines 2024, 12, 146. https://doi.org/10.3390/biomedicines12010146
Xagara A, Roumeliotou A, Kokkalis A, Tsapakidis K, Papakonstantinou D, Papadopoulos V, Samaras I, Chantzara E, Kallergi G, Kotsakis A. ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment. Biomedicines. 2024; 12(1):146. https://doi.org/10.3390/biomedicines12010146
Chicago/Turabian StyleXagara, Anastasia, Argyro Roumeliotou, Alexandros Kokkalis, Konstantinos Tsapakidis, Dimitris Papakonstantinou, Vassilis Papadopoulos, Ioannis Samaras, Evagelia Chantzara, Galatea Kallergi, and Athanasios Kotsakis. 2024. "ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment" Biomedicines 12, no. 1: 146. https://doi.org/10.3390/biomedicines12010146
APA StyleXagara, A., Roumeliotou, A., Kokkalis, A., Tsapakidis, K., Papakonstantinou, D., Papadopoulos, V., Samaras, I., Chantzara, E., Kallergi, G., & Kotsakis, A. (2024). ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment. Biomedicines, 12(1), 146. https://doi.org/10.3390/biomedicines12010146