Preview

INCREASE IN NKT CELLS – A MARKER OF EARLY PROGRESSING AT ADJUVANTVACCINOTHERAPY OF PATIENTS WITH A METASTATIC MELANOMA OF SKIN

https://doi.org/10.17650/1726-9784-2019-18-4-82-89

Abstract

Introduction. Natural killer T lymphocytes (NKT) take place between the innate and acquired immune response. The ability of these cells to activate the antitumor immune response and inhibit immunological activity makes them the target of research in cancer patients. The radicality of surgical treatment of patients with metastatic melanoma (stage III–IV) is relatively conventional. In this regard, the possibility of adjuvant effective therapy of melanoma is actively investigated worldwide.

The aim of the study is investigation of the importance of increasing the number of NKT cells in the peripheral blood of patients with metastatic melanoma after radical surgical removal of the tumor. Patients were treated with adjuvant regimen antitumor autologous dendritic cell therapy in form of vaccination.

Materials and methods. The study included 39 patients with stage III and IV metastatic melanoma with regional and / or distant metastases after radical surgery. From the peripheral blood monocytes of each patient, an autologous vaccine was created from mature dendritic cells loaded with tumor lysate. The therapy continued until objective progression. The study included patients who received from 5 to 120 injections. The follow-up period ranged from 5 to 168 months.

Results. It was shown that 14 (36 %) of patients had the number of NKT cells exceeding the norm (0–10 %) and in the course of vaccine therapy they had the progression of the disease in the period up to 2 years. In patients with relapse-free course of the disease in vaccine therapy (n = 13), the number of NKT lymphocytes did not exceed the norm both before and during therapy. Significantly shorter time to progression was revealed in patients with high initial content of NKT lymphocytes compared with patients with normal indices of NKT cells (6.5 months) – 95 % confidence limit 2,4–10,7 % vs 96,2 months (95 % confidence limit 63.8–128.6 %). 

Conclusion. An increased number of NKT cells in patients with stage III–IV metastatic melanoma after radical surgical treatment is a marker of early progression.

About the Authors

A. A. Borunova
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


G. Z. Chkadua
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


T. N. Zabotina
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


Z. G. Kadagidze
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


O. V. Korotkova
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


A. I. Chertkova
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


D. V. Tabakov
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


E. N. Zakharova
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


E. K. Shoua
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


N. N. Petenko
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


L. V. Demidov
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


I. N. Mikhailova
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia


References

1. Bendelac A., Savage P. B., Teyton L. The biology of NKT cells. Annu Rev Immunol 2007;25:297–336. DOI: 10.1146/annurev.immunol.25.022106.141711.

2. Godfrey D. I., Stankovic S., Baxter A. G. Raising the NKT cell family. Nature Immunol 2010;11(3):197–206. DOI: 10.1038/ni.1841.

3. Akinfeeva O. V., Bubnova L. N., Bessmeltsev S. S. NKT cells: characteristic features and functional significance in the immune response regulation. Onkogematologiya = Oncohematology 2010;5(4):39–47. (In Russ.)

4. Nair S., Dhodapkar M. V. Natural killer T cells in cancer immunotherapy. Front Immunol 2017;8:(1178). DOI: 10.3389/fimmu.2017.01178.

5. Godfrey D. I., Kronenberg M. Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 2004;114(10):1379–88. DOI: 10.1038/nri11309.

6. Kwak M., Farrow N. E., Salama A. K.S. et al. Updates in adjuvant systemic therapy for melanoma. J Surg Oncol 2019;119(2): 222–321. DOI: 10.1002/jso.25298.

7. Boudewijns S., Bloemendal M., Gerritsen W. R. et al. Dendritic cell vaccination in melanoma patients: From promising results to future perspectives. Hum Vaccin Immunother 2016;12(10):2523–8. DOI: 10.1080/21645515.2016.1197453.

8. Stroyakovsky D. L., Abramov M. E., Demidov L. V. et al. Practical recommendations for drug treatment of skin melanoma. Malignant tumors: Practical recommendations of RUSSCO RUSSCO 2017;7(3 Suppl. 2):190–202. (In Russ.) DOI: 10.18027/2224-5057-2017-7-3s2-190-202.

9. Stroyakovsky D. L., Abramov M. E., Demidov L. V. et al. Practical recommendations for drug treatment of skin melanoma. Malignant tumors: Practical recommendations of RUSSCO2018;8(3 Suppl. 2):212–26. DOI: 10.18027/2224-5057-2018-8-3s2-213-26. (In Russ.) DOI: 10.18027/2224-5057-2018-8-3s2-213-226.

10. Bello D. M., Ariyan C. E. Adjuvant Therapy in the Treatment of Melanoma. Ann Surg Oncol 2018;25(7):1807–13. DOI: 10.1245/s10434‑018‑6376-y.

11. Garg A. D., Vara Perez M., Schaaf M. et al. Trial watch: dendritic cell-based anticancer immunotherapy. Oncoimmunology 2017;6(7):1328341. DOI: 10.1080/2162402X.2017.1328341.

12. Dillman R. O., Nistor G. I., Cornforth A. N. Dendritic cell vaccines for melanoma: past, present and future. Melanoma Manag 2016;3(4):273–89. DOI: 10.2217/mmt-2016-0014.

13. Baldueva I. A., Novik A. V., Gelfond M. L. et al. Dendritic-Cell Immunotherapy in Combination with Photodynamic Therapy and Cyclophosphamide in Patients with Metastatic Melanoma, Resistant to Standard Methods of Treatment. Effective Pharmacotherapy. Oncology, Hematology & Radiology. Special Issue “Melanoma”. 2017;36:32–41. (In Russ.)

14. Ridolfi L., de Rosa F., Fiammenghi L. A. et al. Complementary vaccination protocol with dendritic cells pulsed with autologous tumour lysate in patients with resected stage III or IV melanoma: protocol for a phase II randomised trial (ACDC Adjuvant Trial). BMJ Open 2018;8(8):021701. DOI: 10.1136/bmjopen-2018-021701.

15. Chertkova A. I., Slavina E. G., Shoua E. K. et al. The main parameters of cellular immunity in patients with triple-negative breast cancer: Relationship with efficiency of chemotherapy Meditsinskaya Immunologiya = Medical Immunology 2018;20(5):667–80. (In Russ.) DOI: 10.15789/1563‑0625‑2018‑5.


Review

For citations:


Borunova A.A., Chkadua G.Z., Zabotina T.N., Kadagidze Z.G., Korotkova O.V., Chertkova A.I., Tabakov D.V., Zakharova E.N., Shoua E.K., Petenko N.N., Demidov L.V., Mikhailova I.N. INCREASE IN NKT CELLS – A MARKER OF EARLY PROGRESSING AT ADJUVANTVACCINOTHERAPY OF PATIENTS WITH A METASTATIC MELANOMA OF SKIN. Russian Journal of Biotherapy. 2019;18(4):82-89. (In Russ.) https://doi.org/10.17650/1726-9784-2019-18-4-82-89

Views: 604


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1726-9784 (Print)
ISSN 1726-9792 (Online)