Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Clinicopathological Cohort Characteristics
2.2. Tissue Microarray and Immunohistochemistry
2.3. PD-L1 Evaluation
2.4. Evaluation of CD4, CD8, PD-1, TIGIT and CD155
2.5. Statistical Analysis
3. Results
3.1. PD-L1 Expression in Gallbladder Cancer
3.2. PD-L1 Expression in High-Grade Biliary Intraepithelial Neoplasia
3.3. Correlation of PD-L1 Expression with Clinicopathological Criteria
3.4. Correlation of PD-L1 Expression with MHC I Expression and HER2 Amplification
3.5. High Tumoral PD-L1 Expression Is Associated with Worse Survival
3.6. PD-L1 Expression Is Associated with Increased CD4+-, CD8+- and PD-1+ Immune Cell Densities
3.7. Expression of the Inhibitory Immune Receptor TIGIT and Its Ligand CD155
3.8. CD155 Is a Negative Prognosticator in Western-World Gallbladder Cancer
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Project Number
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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PD-L1 | <1% | 1–9% | 10–24% | >25% |
---|---|---|---|---|
TPS | 110 (85%) | 13 (10%) | 2 (2%) | 4 (3%) |
IC | 86 (67%) | 23 (18%) | 16 (12%) | 4 (3%) |
CPS | 84 (65%) | 19 (15%) | 13 (10%) | 13 (10%) |
Characteristic | PD-L1 neg. (TPS < 10%) | PD-L1 pos. (TPS ≥ 10%) | p-Value |
---|---|---|---|
GBC patients | 123 (95.3%) | 6 (4.7%) | |
Age (years) | 72.9 (63.6–78.8) | 78.55 (65.2–82.8) | 0.42 |
Sex | |||
female | 80 (35.0) | 6 (100%) | 0.18 |
male | 43 (65.0%) | 0 (0%) | |
Histology | |||
NOS | 61 (49.6%) | 2 (33.3%) | * 0.046 |
mucinous | 19 (15.4%) | 0 (0%) | |
adenosquamous | 15 (12.2%) | 1 (16.7%) | |
signet ring | 15 (12.2%) | 1 (16.7%) | |
papillary | 10 (8.1%) | 0 (0.0%) | |
solid | 1 (0.8%) | 2 (33.3%) | |
intestinal | 2 (1.6%) | 0 (0.0%) | |
UICC | |||
1 | 0 (0%) | 0 (0%) | * 0.59 |
2 | 15 (15.2%) | 0 (0%) | |
3 | 58 (58.6%) | 6 (100%) | |
4 | 26 (26.3%) | 0 (0%) | |
NA | 24 | 0 | |
pT | |||
1 | 6 (4.9%) | 0 (0%) | * 0.22 |
2 | 52 (42.3%) | 1 (16.7%) | |
3 | 57 (46.3%) | 5 (83.3%) | |
4 | 8 (6.5%) | 0 (0%) | |
pN | |||
0 | 27 (42.9%) | 1 (50.0%) | 0.98 |
1 | 36 (57.1%) | 1 (50.0%) | |
X | 60 | 4 | |
pM | |||
1 | 22 (17.9%) | 0 (0%) | 0.59 |
X | 101 (82.1%) | 6 (100%) | |
L | |||
0 | 47 (38.2%) | 1 (16.7%) | 0.41 |
1 | 76 (61.8%) | 5 (83.3%) | |
V | |||
0 | 57 (46.3%) | 2 (33.3%) | 0.69 |
1 | 66 (53.7%) | 4 (66.7%) | |
Pn | |||
0 | 63 (51.2%) | 2 (33.3%) | 0.68 |
1 | 60 (48.8%) | 4 (66.7%) | |
R | |||
0 | 46 (46.5%) | 3 (60.0%) | * 0.66 |
1 | 47 (47.5%) | 2 (40.0%)1 | |
2 | 6 (6.1%) | 0 (0%) | |
X | 24 | 1 | |
Grading | |||
G1 | 5 (4.1%) | 0 (0%) | * 0.024 |
G2 | 76 (61.8%) | 1 (16.7%) | |
G3 | 42 (34.1%) | 5 (83.3%) |
TPS | <10% | ≥10% |
---|---|---|
NOS | 97% | 3% |
Mucinous | 100% | 0% |
Adenosquamous | 94% | 6% |
Signet ring | 94% | 6% |
Papillary | 100% | 0% |
Solid | 33% | 67% |
Intestinal | 100% | 0% |
Variable | Groups | HR | Lower CI (95%) | Upper CI (95%) | p-Value |
---|---|---|---|---|---|
TPS | TPS < 10% | 1 | - | - | - |
TPS ≥ 10% | 9.404 | 1.733 | 51.020 | 0.009 | |
UICC stage | UICC 2 | 1 | - | - | - |
UICC 3 | 4.649 | 1.320 | 16.372 | 0.017 | |
UICC 4 | 5.469 | 1.468 | 20.375 | 0.011 |
Authors [Reference] | Country | Study Design | Agent | No of Patients | No of GBC Patients | Outcome |
---|---|---|---|---|---|---|
Bang et al. [33] | Japan | Phase Ib | Pembrolizumab | 24 | - | 13% PR, mPFS 1.8 mos, mOS 6.2 mos. |
Bang et al. [33] | Japan | Phase II | Pembrolizumab | 104 | - | 5.8% PR, mPFS 2.0 mos, mOS 7.4 mos. |
Ueno et al. [34] | Japan | Phase I | Nivolumab + cisplatin + gemcitabine | 30 | 10 | 36.7% PR, mPFS 4.2 mos., mOS 15.4 mos. |
Ueno et al. [34] | Japan | Phase II | Nivolumab | 30 | 10 | 3% PR, mPFS 1.4 mos., mOS 5.2 mos |
Kim et al. [38] | USA | Phase II | Nivolumab | 54 | 14 | 22% PR, mPFS 3.98 mos., mOS 14.22 mos. |
Ioka et al. [35] | Japan | Phase I | Durvalumab + tremelimumab | 65 | 16 | 10.8 % PR, mPFS 1.6 mos., mOS 10.1 mos. |
Ioka et al. [35] | Japan | Phase II | Durvalumab | 42 | 19 | 4.8 % PR, mPFS 1.5 mos., mOS 8.1 mos. |
Fujiwara et al. [37] | Japan | Phase I | M7824 (MSB0011359C) | 30 | 12 | 25% PR * |
Yoo et al. [36] | USA | Phase I | Tremelimumab + RFA | 16 | 2 | 12.5% PR, mPFS 3.4 mos., mOS 6.0 mos. |
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Albrecht, T.; Brinkmann, F.; Albrecht, M.; Lonsdorf, A.S.; Mehrabi, A.; Hoffmann, K.; Kulu, Y.; Charbel, A.; Vogel, M.N.; Rupp, C.; et al. Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer. Cancers 2021, 13, 1682. https://doi.org/10.3390/cancers13071682
Albrecht T, Brinkmann F, Albrecht M, Lonsdorf AS, Mehrabi A, Hoffmann K, Kulu Y, Charbel A, Vogel MN, Rupp C, et al. Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer. Cancers. 2021; 13(7):1682. https://doi.org/10.3390/cancers13071682
Chicago/Turabian StyleAlbrecht, Thomas, Fritz Brinkmann, Michael Albrecht, Anke S. Lonsdorf, Arianeb Mehrabi, Katrin Hoffmann, Yakup Kulu, Alphonse Charbel, Monika N. Vogel, Christian Rupp, and et al. 2021. "Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer" Cancers 13, no. 7: 1682. https://doi.org/10.3390/cancers13071682