BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine
Abstract
:1. Introduction
2. Results
2.1. Rationale for Study Design
2.2. NMIBC Patients Release Immune Mediators One Week after BCG Instillation
2.3. CXCL10 (IP10) Is Highly Secreted in BCG-Treated NMIBC Patients Seven Days after the Instillations
2.4. Urinary CXCL10 Is Produced by Myeloid Cells
2.5. CXCL10 Does Not Increase the Percentage of Anti-Tumour CD56bright Cells, but Facilitates in the Migration of BCG-Activated Effector Cells
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Sample Handling
4.3. Creatinine Determination
4.4. Cytokine Measurements
4.5. Statistical Analyses
4.6. IP10 Stimulation of PBMCs
4.7. Flow Cytometry
4.8. Peripheral Blood Mononuclear Cell Stimulation with BCG
4.9. Migration Experiments
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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BCG | MMC | ||||
---|---|---|---|---|---|
N | % | N | % | ||
Gender | Male | 10 | 83.3 | 4 | 66.7 |
Female | 2 | 16.7 | 2 | 33.3 | |
Age | 60 or less | 2 | 16.7 | 0 | 0.0 |
61–70 | 6 | 50.0 | 5 | 83.3 | |
more than 71 | 4 | 33.3 | 1 | 16.7 | |
Size | <3 cm | 8 | 66.7 | 2 | 33.3 |
≥3 cm | 3 | 25.0 | 4 | 66.7 | |
N/A | 1 | 8.3 | |||
Number | <3 | 7 | 58.3 | 5 | 83.3 |
≥3 | 4 | 33.3 | 1 | 16.7 | |
N/A | 1 | 8.3 | |||
Primary | 11 | 91.7 | 6 | 100.0 | |
Recurrent | 1 | 8.3 | 0 | 0.0 | |
CIS | 5 | 41.7 | |||
T1 | 7 | 58.3 | 4 | 66.7 | |
Ta | 3 | 25.0 | 2 | 33.3 | |
G1 | 0 | 0.0 | 1 | 16.7 | |
G2 | 1 | 8.3 | 5 | 83.3 | |
G3 | 10 | 83.3 | 0 | 0.0 | |
Treatment delayed as a result of side effects | 4 | 33.3 | 0 | 0.0 | |
Stop as a result of side effects | 1 | 8.3 | 0 | 0.0 | |
Recurrence—n (%) | 4 | 33.3 | 0 | 0.0 | |
Progression | 1 | 8.3 | 0 | 0.0 |
Patient | Tumor | Stop/Delay | Recurrence | Progression |
---|---|---|---|---|
P7 | Primary | After B1.6 as a result of discomfort | After B1.6, TUR Restart BCG with delay | |
P8 | Previous tumors in 1990, 1995 | 2.7 years after B1.1 T4a | ||
P15 | Primary | Delay after B3.2 as a result of prostate treatment | 2.4 years from B1.1: 2 × T1G2; 5 years from B1.1: 3 × TxGx | |
P17 | Previous TaG2 | After B6.1 as a result of cystitis | 3.1 years from B1.1 TxGx |
Cytokine/Chemokine | Limit * (pg/mL) | BCG # | Mitomycin # | Healthy |
---|---|---|---|---|
IL-1β | 10.0 | 3/12 | - | - |
IL-2 | 28.03 | 5/12 | 4/6 | - |
IL-4 | 16.87 | - | - | - |
IL-5 | 14.59 | - | - | - |
IL-6 | 20.08 | 6/12 | 3/6 | - |
IL-8 | 17.74 | 7/12 | 5/6 | - |
IL-9 | 2414.91 | - | - | - |
IL-10 | 14.81 | - | - | - |
IL-12p70 | 249.14 | - | - | - |
IL-15 | 8.18 | - | - | - |
IL-17 | 18.64 | - | - | - |
IL-18BPa | 32.55 | + | + | + |
IL-22 | 17.49 | 2/12 | - | + |
IL-23 | 293.58 | 1/12 | - | - |
TNF-α | 19.75 | - | - | - |
IFN-γ | 6.3 | - | - | - |
MIP1β | 48.23 | - | - | - |
MIG | 843.21 | - | - | - |
CXCL10 | 3.54 | 11/12 | 2/6 | - |
RANTES | 14.53 | 5/12 | 1/6 | - |
TRAIL | 34.98 | + | + | + |
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Ashiru, O.; Esteso, G.; García‐Cuesta, E.M.; Castellano, E.; Samba, C.; Escudero-López, E.; López‐Cobo, S.; Álvarez-Maestro, M.; Linares, A.; Ho, M.M.; et al. BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine. Cancers 2019, 11, 940. https://doi.org/10.3390/cancers11070940
Ashiru O, Esteso G, García‐Cuesta EM, Castellano E, Samba C, Escudero-López E, López‐Cobo S, Álvarez-Maestro M, Linares A, Ho MM, et al. BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine. Cancers. 2019; 11(7):940. https://doi.org/10.3390/cancers11070940
Chicago/Turabian StyleAshiru, Omodele, Gloria Esteso, Eva M. García‐Cuesta, Eva Castellano, Celia Samba, Eva Escudero-López, Sheila López‐Cobo, Mario Álvarez-Maestro, Ana Linares, Mei M. Ho, and et al. 2019. "BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine" Cancers 11, no. 7: 940. https://doi.org/10.3390/cancers11070940
APA StyleAshiru, O., Esteso, G., García‐Cuesta, E. M., Castellano, E., Samba, C., Escudero-López, E., López‐Cobo, S., Álvarez-Maestro, M., Linares, A., Ho, M. M., Leibar, A., Martínez‐Piñeiro, L., & Valés‐Gómez, M. (2019). BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine. Cancers, 11(7), 940. https://doi.org/10.3390/cancers11070940