Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Immune Cell Analysis
2.3. Response and Survival Analysis
3. Results
3.1. Patients and Immune Cell Analysis
3.2. Response to Treatment and Survival Outcomes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Antibody Name | Catalog No. | Antibody Volume (µL) | |
---|---|---|---|
Panel 1 | CD4-BV421 | 562,424 | 0.3 (T4) |
CD3-BV510 | 564,713 | 0.6 (T3) | |
CD8-BV650 | 563,821 | 0.3 (T4) | |
CD14-FITC | 347,493 | 0.2 (1:100) | |
NKp46-PE | 557,991 | 5 (T2) | |
CD19-BB700 | 566,397 | 0.6 (T3) | |
CD56-PE-Cy7 | 557,747 | 1.2 (T2) | |
CD16-AF647 | 557,710 | 0.05 (1:100) | |
Panel 2 | CD4-BV421 | 562,424 | 0.3 (T4) |
CD3-BV510 | 564,713 | 0.6 (T3) | |
CD8-BV650 | 563,821 | 0.3 (T4) | |
PD-1-FITC | 557,860 | 2 (T1) | |
CTLA4-PE | 555,853 | 5 (T2) | |
CD39-PerCP-Cy5.5 | 564,899 | 1.2 (T2) | |
Ki-67-PE-Cy7 | 561,283 | 1.2 (T2) | |
GranzymeB-AF647 | 560,212 | 0.1 (1:50) |
Panel 1 | Surface Stains | ||||||||
---|---|---|---|---|---|---|---|---|---|
FVS 780 (565,388) | CD3 BV510 (564,713) | CD4 BV421 (562,424) | CD8 BV650 (563,821) | CD14 FITC (347,493) | NKp46 PE (557,991) | CD19 BB700 (566,396) | CD56 PE-Cy7 (557,747) | CD16 AF647 (557,710) | |
1. Unstained PBMC compensation control | NA | NA | NA | NA | NA | NA | NA | NA | NA |
2. Killed PBMC FVS780 viability compensation control | 1:1000 | NA | NA | NA | NA | NA | NA | NA | NA |
3. NKp46 FMO | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 10 µL * | NA | 0.6 µL | 1.2 µL | 2.5 µL * |
4. CD16 FMO | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 10 µL * | 5 µL | 0.6 µL | 1.2 µL | NA * |
5. CD56 FMO | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 10 µL * | 5 µL | 0.6 µL | NA | 2.5 µL * |
6. All Stains | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 10 µL * | 5 µL | 0.6 µL | 1.2 µL | 2.5 µL * |
Panel 2 | Surface Stains | Intracellular Stains | |||||||
---|---|---|---|---|---|---|---|---|---|
FVS 780 (565,388) | CD3 BV510 (564,713) | CD4 BV421 (562,424) | CD8 BV650 (563,821) | PD-1 FITC (557,860) | CD39-PerCP-Cy5.5 (564,899) | CTLA4 PE (555,853) | Ki-67-PE-Cy7 (561,283) | GranzymeB-AF647 (560,212) | |
1. Unstained PBMC compensation control | NA | NA | NA | NA | NA | NA | NA | NA | NA |
2. Killed PBMC FVS780 viability compensation control | 1:1000 | NA | NA | NA | NA | NA | NA | NA | NA |
3. PD-1 FMO | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | NA | 1.2 µL | 5 µL | 1.2 µL | 5 µL * |
4. CD39 FMO | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 2 µL | NA | 5 µL | 1.2 µL | 5 µL * |
5. CTLA4 FMO | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 2 µL | 1.2 µL | NA | 1.2 µL | 5 µL * |
6. Ki-67 FMO | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 2 µL | 1.2 µL | 5 µL | NA | 5 µL * |
7. Granzyme B FMO | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 2 µL | 1.2 µL | 5 µL | 1.2 µL | NA * |
8. All Stains | 1:1000 | 0.6 µL | 0.3 µL | 0.3 µL | 2 µL | 1.2 µL | 5 µL | 1.2 µL | 5 µL * |
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Variables (n = 90) | No. of Patients (%) |
---|---|
Median age (years) (range) | 65.0 (26 to 84) |
Sex | |
Male | 55 (61.1%) |
Female | 35 (38.9%) |
ECOG performance status | |
0 | 10 (11.1%) |
1 | 78 (86.7%) |
2 | 2 (2.2%) |
Type of cancer | |
Lung cancer | 45 (50.0%) |
Others † | 45 (50.0%) |
Previous lines of treatment | |
0 | 13 (14.4%) |
1 | 41 (45.6%) |
2 | 22 (24.4%) |
≥3 | 14 (15.6%) |
Immune checkpoint inhibitor | |
Pembrolizumab | 36 (40.0%) |
Nivolumab | 40 (44.4%) |
Atezolizumab | 14 (15.6%) |
Durvalumab | - |
Combined chemotherapy | |
Yes ‡ | 2 (2.2%) |
No | 88 (97.8%) |
Type of Immune Cells | Median Value of Change (%) (Range) |
---|---|
Panel 1 | |
CD4+ T cell | −1.95 (−36.20 to 31.60) |
CD8+ T cell | 1.55 (−27.40 to 32.50) |
CD14+ monocyte | −0.51 (−34.90 to 43.60) |
CD19+ B cell | −0.27 (−6.90 to 10.38) |
Q1: CD16−/CD56+ | −0.45 (−17.20 to 11.31) |
Q2: CD16+/CD56+ | 4.05 (−37.10 to 48.58) |
Q3: CD16+/CD56− | 0.33 (−18.80 to 11.17) |
Q4: CD16−/CD56− | −4.00 (−49.60 to 42.80) |
Q5: NKp46−/CD56+ | 0.30 (−24.80 to 20.50) |
Q6: Kp46+/CD56+ | 1.45 (−28.14 to 33.90) |
Q7: NKp46+/CD56− | 0.12 (−3.25 to 4.24) |
Q8: NKp46−/CD56− | −4.60 (−51.60 to 43.10) |
Panel 2 | |
PD-1+ CD4+ | −5.49 (−30.60 to 24.77) |
CTLA4+ CD4+ | 1.25 (−12.30 to 27.80) |
CD39+ CD4+ | 0.29 (−6.50 to 12.71) |
Ki-67+ CD4+ | 0.45 (−8.66 to 6.90) |
GrB+ CD4+ | 0.96 (−26.82 to 24.30) |
PD-1+ CD8+ | −5.31 (−31.47 to 42.57) |
CTLA4+ CD8+ | 0.71 (−13.10 to 32.20) |
CD39+ CD8+ | 0.37 (−19.67 to 17.11) |
Ki-67+ CD8+ | 0.53 (−14.80 to 20.60) |
Variables (n = 90) | Value |
---|---|
Best response | |
CR | - |
PR | 13 (14.4%) |
SD | 32 (35.6%) |
PD | 34 (37.8%) |
Unknown | 11 (12.2%) |
ORR | 13 (14.4%) |
CBR | 45 (50.0%) |
Median treatment cycle (range) | 5 (1 to 28) |
Median treatment duration (months) (IQR) | 2.40 (1.31 to 5.53) |
Median PFS (months) (95% CI) | 6.00 (3.11 to 8.89) |
Median OS (months) (95% CI) | 13.90 (5.62 to 22.19) |
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Kim, H.R.; Kang, J.H.; Kim, S.H.; Kim, S.T.; Kim, I.; Min, Y.J.; Shin, S.H.; Oh, S.Y.; Lee, G.-W.; Lee, J.H.; et al. Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors. Cancers 2022, 14, 3440. https://doi.org/10.3390/cancers14143440
Kim HR, Kang JH, Kim SH, Kim ST, Kim I, Min YJ, Shin SH, Oh SY, Lee G-W, Lee JH, et al. Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors. Cancers. 2022; 14(14):3440. https://doi.org/10.3390/cancers14143440
Chicago/Turabian StyleKim, Hye Ryeon, Jung Hun Kang, Sung Hyun Kim, Seung Tae Kim, Ilhwan Kim, Young Joo Min, Seong Hoon Shin, Sung Yong Oh, Gyeong-Won Lee, Ji Hyun Lee, and et al. 2022. "Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors" Cancers 14, no. 14: 3440. https://doi.org/10.3390/cancers14143440