Skip to main content

Advertisement

SpringerLink
Log in

Immunotherapy with autologous dendritic cells in the complex treatment of malignant gliomas - results

  • Research
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Annotation

Malignant gliomas are the most common primary brain tumor. Despite the variety of modern treatments, it is still a fatal disease with an extremely poor prognosis. The use of immunotherapy as a technique for the treatment of malignant tumors has great promise, retraining and exploiting the patient’s immune response against tumors.

Objective

Evaluation of the effectiveness of dendritic cell vaccine in patients with malignant brain gliomas in the structure of complex treatment in comparison with the control group of patients without immunotherapy in the structure of treatment.

Materials and methods

In a single-center, prospective, cohort study, taking place on the basis of the RNSI named after prof. A.L. Polenov, 91 patients with morphologically established malignant glial tumor (glioblastoma) took part. The main group of 41 patients who, in addition to standard treatment (surgical, radiation and chemotherapy), underwent specific antitumor immunotherapy. 50 patients received only standard treatment, without immunotherapy.

Results

Median survival was 21.7 months in the immunotherapy group (95% CI 4–37 months) and 15.8 months (95% CI 3–22 months) in the non-immunotherapy group (p = 0.002). The median relapse-free period in the group with immunotherapy was 13.8 months (95% CI 1–20 months), and in the group without immunotherapy 7.9 months (95% CI 1–12 months) (p = 0.003).

Conclusion

In general, the use of immunotherapy in the structure of complex treatment of patients with malignant gliomas demonstrates a clear positive trend in terms of overall survival and median relapse-free period. But nevertheless, immunotherapy requires further development as a therapeutic tool, study and improvement, which will take into account immunosuppression in malignant gliomas and means of overcoming it, optimization in terms of target antigen selection, cell preparation and integration of dendritic vaccines into other treatment regimens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS (2021) CBTRUS Statistical Report: primary brain and other Central Nervous System tumors diagnosed in the United States in 2014–2018. Neuro Oncol 23:III1–III105. https://doi.org/10.1093/NEUONC/NOAB200

    Article  PubMed  PubMed Central  Google Scholar 

  2. Poon MTC, Sudlow CLM, Figueroa JD, Brennan PM (2020) Longer-term (≥ 2 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: a systematic review and meta-analysis. Sci Rep 10:11622. https://doi.org/10.1038/s41598-020-68011-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ostrom QT, Cote DJ, Ascha M, Kruchko C, Barnholtz-Sloan J (2018) Adult glioma incidence and survival by race or ethnicity in the United States from 2000 to 2014. JAMA Oncol 4:1254–1262. https://doi.org/10.1001/jamaoncol.2018.1789

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rynda AYu, Olyushin VE, Rostovtsev DM, Zabrodskaya YM, Tastanbekov MM, Papayan GV (2021) Intraoperative fluorescence control with chlorin E6 in resection of glial brain tumors. Zhurnal Voprosy Neirokhirurgii Imeni N N Burdenko 85(4):20–28 (In Russ.). https://doi.org/10.17116/neiro20218504120

    Article  Google Scholar 

  5. Rynda AYu, Olyushin VE, Rostovtsev DM, Zabrodskaya YM, Ulitin AYu, Papayan GV (2023) Intraoperative photodynamic therapy in complex treatment of malignant gliomas. Burdenko’s Journal of Neurosurgery = Zhurnal Voprosy neirokhirurgii imeni N. N Burdenko 87(1):25–34 (In Russ.). https://doi.org/10.17116/neiro20238701125

    Article  Google Scholar 

  6. Rynda AYu, Olyushin VE, Rostovtsev DM, Zabrodskaya YM, Papayan GV (2022) Comparative analysis of 5-ALA and chlorin E6 fluorescence-guided navigation in malignant glioma Surgery. Pirogov Russian Journal of Surgery = Khirurgiya Zurnal Im N I Pirogova 15–14 (In Russ.). https://doi.org/10.17116/hirurgia20220115

  7. Chekhonin IV, Kobiakov GL, Gurina OI (2020) Dendritic cell vaccines in neurological oncology. Zhurnal Voprosy Neirokhirurgii Imeni N N Burdenko 84(1):76–85 (In Russ.). https://doi.org/10.17116/neiro20208401176

    Article  CAS  PubMed  Google Scholar 

  8. Medikonda R, Dunn G, Rahman M, Fecci P, Lim M (2020) A review of glioblastoma immunotherapy. J Neuro-Oncol 151:41–53. https://doi.org/10.1007/s11060-020-03448-1

    Article  Google Scholar 

  9. Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, Chumsri S, Lou Y (2018) Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol 11:39. https://doi.org/10.1186/s13045-018-0582-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Barrueto L, Caminero F, Cash L, Makris C, Lamichhane P, Deshmukh RR (2020) Resistance to checkpoint inhibition in cancer immunotherapy. Transl Oncol 13:100738. https://doi.org/10.1016/j.tranon.2019.12.010

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chauvin J-M, Zarour HM (2020) TIGIT in cancer immunotherapy. J Immunother Cancer 8:e000957. https://doi.org/10.1016/10.1136/jitc-2020-000957

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kim JE, Lim M (2015) The role of checkpoints in the treatment of GBM. J Neuro-Oncol 123:413–423. https://doi.org/10.1007/s11060-015-1747-8

    Article  CAS  Google Scholar 

  13. Bao Z, Wang Y, Wang Q, Fang S, Shan X, Wang J et al (2021) Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and evolution. Front Med 15:551–561. https://doi.org/10.1007/s11684-020-0760-2

    Article  PubMed  Google Scholar 

  14. Andersen RS, Anand A, Harwood DSL, Kristensen BW (2021) Tumor-associated microglia and macrophages in the glioblastoma microenvironment and their implications for therapy. Cancers 13:4255. https://doi.org/10.3390/cancers13174255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rynda A, Olyushin V, Rostovtsev D (2021) Immunotherapy in the complex treatment of HGG. Neurooncology 23(2):i47. https://doi.org/10.1093/neuonc/noab180.164

    Article  Google Scholar 

  16. Datsi A, Sorg RV (2021) Dendritic cell vaccination of Glioblastoma: Road to Success or Dead End. Front Immunol 12:770390. https://doi.org/10.3389/fimmu.2021.770390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liau LM, Black KL, Martin NA, Sykes SN, Bronstein JM, Jouben-Steele L et al (2000) Treatment of a patient by Vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I-Matched Tumor peptides. Case Rep Neurosurg Focus 9:e8. https://doi.org/10.3171/foc.2000.9.6.9

    Article  CAS  Google Scholar 

  18. Burster T, Gärtner F, Bulach C, Zhanapiya A, Gihring A, Knippschild U (2021) Regulation of MHC I molecules in glioblastoma cells and the sensitizing of NK cells. Pharmaceuticals 14:236. https://doi.org/10.3390/ph14030236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hung AL, Maxwell R, Theodros D, Belcaid Z, Mathios D, Luksik AS et al (2018) TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM. Oncoimmunology 7(8):e1466769. https://doi.org/10.1080/2162402X.2018.1466769

    Article  PubMed  PubMed Central  Google Scholar 

  20. Litak J, Mazurek M, Grochowski C, Kamieniak P, Roliński J (2019) PD-L1/PD-1 axis in Glioblastoma Multiforme. Int J Mol Sci 20:5347. https://doi.org/10.3390/ijms20215347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wu A, Maxwell R, Xia Y, Cardarelli P, Oyasu M, Belcaid Z et al (2019) Combination anti-CXCR4 and anti-PD-1 immunotherapy provides survival benefit in glioblastoma through immune cell modulation of Tumor microenvironment. J Neuro Oncol 143:241–249. https://doi.org/10.1007/s11060-019-03172-5

    Article  CAS  Google Scholar 

  22. Yu JS, Wheeler CJ, Zeltzer PM et al (2001) Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res 61:842–847

    CAS  PubMed  Google Scholar 

  23. Chan HY, Choi J, Jackson C, Lim M (2021) Combination immunotherapy strategies for glioblastoma. J Neuro-Oncol 151:375–391. https://doi.org/10.1007/s11060-020-03481-0

    Article  Google Scholar 

  24. Lamano JB, Lamano JB, Li YD, DiDomenico JD, Choy W, Veliceasa D et al (2019) Glioblastoma-derived IL6 induces immunosuppressive peripheral myeloid cell PD-L1 and promotes Tumor growth. Clin Cancer Res 25:3643–3657. https://doi.org/10.1158/1078-0432.CCR-18-2402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bausart M, Préat V, Malfanti A (2022) Immunotherapy for glioblastoma: the promise of combination strategies. J Exp Clin Cancer Res 41:35. https://doi.org/10.1186/s13046-022-02251-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jin K, Mao C, Chen L, Wang L, Liu Y, Yuan J (2021) Adenosinergic pathway: a hope in the immunotherapy of glioblastoma. Cancers 13:229. https://doi.org/10.3390/cancers13020229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Olyushin V, Rynda A, Rostovtsev D (2020) Immunotherapy with autologous dendritic cells as part of the complex treatment of patients with malignant gliomas. Ann Oncol 31(4):S405. https://doi.org/10.1016/j.annonc.2020.08.493

    Article  Google Scholar 

  28. Yao Y, Luo F, Tang C, Chen D, Qin Z, Hua W et al (2018) Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in Glioblastoma: an exploratory Randomized Phase II Clinical Trial. Cancer Immunol Immunother 67:1777–1788. https://doi.org/10.1007/s00262-018-2232-y

    Article  CAS  PubMed  Google Scholar 

  29. Cho DY, Yang WK, Lee HC, Hsu DM, Lin HL, Lin SZ et al (2012) Adjuvant immunotherapy with whole-cell lysate dendritic cells vaccine for Glioblastoma Multiforme: a phase II clinical trial. World Neurosurg 77:736–744. https://doi.org/10.1016/j.wneu.2011.08.020

    Article  PubMed  Google Scholar 

  30. Wen PY, Reardon DA, Armstrong TS, Phuphanich S, Aiken RD, Landolfi JC et al (2019) A Randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine Ict-107 in newly diagnosed patients with Glioblastoma. Clin Cancer Res 25:5799–5807. https://doi.org/10.1158/1078-0432.CCR-19-0261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liau LM, Ashkan K, Tran DD, Campian JL, Trusheim JE, Cobbs CS et al (2018) First results on Survival from a large phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed Glioblastoma. J Transl Med 16:142. https://doi.org/10.1186/s12967-018-1507-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. McGranahan T, Therkelsen KE, Ahmad S, Nagpal S (2019) Current state of immunotherapy for treatment of glioblastoma. Curr Treat Options in Oncol 20:24. https://doi.org/10.1007/s11864-019-0619-4

    Article  Google Scholar 

  33. Jie X, Hua L, Jiang W, Feng F, Feng G, Hua Z (2012) Clinical application of a dendritic cell vaccine raised against Heat-Shocked Glioblastoma. Cell Biochem Biophys 62:91–99. https://doi.org/10.1007/s12013-011-9265-6

    Article  CAS  PubMed  Google Scholar 

  34. Buchroithner J, Erhart F, Pichler J, Widhalm G, Preusser M, Stockhammer G et al (2018) Audencel Immunotherapy based on dendritic cells has no effect on overall and progression-free survival in newly diagnosed glioblastoma: a phase II randomized trial. Cancers (Basel) 10:372. https://doi.org/10.3390/cancers10100372

    Article  CAS  PubMed  Google Scholar 

  35. Louis DN, Perry A, Wesseling P et al (2021) The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol 23(8):1231–1251. https://doi.org/10.1093/neuonc/noab106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Karschnia P, Vogelbaum MA, van den Bent M et al (2021) Evidence-based recommendations on categories for extent of resection in diffuse glioma. Eur J Cancer 149:23–33. https://doi.org/10.1016/j.ejca.2021.03.002

    Article  PubMed  Google Scholar 

  37. Scheffel TB, Grave N, Vargas P, Diz FM, Rockenbach L, Morrone FB (2021) Immunosuppression in gliomas via PD-1/PD-L1 axis and adenosine pathway. Front Oncol 10:617385. https://doi.org/10.3389/fonc.2020.617385

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zhang N, Wei L, Ye M, Kang C, You H (2020) Treatment progress of immune checkpoint blockade therapy for glioblastoma. Front Immunol 11:592612. https://doi.org/10.3389/fimmu.2020.592612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Skaga E, Kulesskiy E, Fayzullin A, Sandberg CJ, Potdar S, Kyttälä A et al (2019) Intertumoral heterogeneity in patient-specific drug sensitivities in treatment-naïve glioblastoma. BMC Cancer 19:628. https://doi.org/10.1186/s12885-019-5861-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The study was performed without external funding.

Author information

Authors and Affiliations

  1. Russian Neurosurgical Institute (RNSI) named after prof. A.L. Polenov– a branch of the National Medical Research Center named after V.A. Almazov »Ministry of Health of Russia, St. Petersburg, Russia

    Artemii Yuryevich Rynda, Dmitrii M. Rostovthev, Yulia M. Zabrodskaya & Victor E. Olyushin

Authors
  1. Artemii Yuryevich Rynda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dmitrii M. Rostovthev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yulia M. Zabrodskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Victor E. Olyushin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by A.R., V.O., D.R. and Yu.Z. The first draft of the manuscript was written by A.R. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Artemii Yuryevich Rynda.

Ethics declarations

Ethical approval

This study was conducted in accordance with the principles of the Declaration of Helsinki. Approval was received by the Ethics Committee of the Russian Research Neurosurgical Institute named after Professor A.L. Polenov (Date 03/07/2013/№ 3577).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rynda, A.Y., Rostovthev, D.M., Zabrodskaya, Y.M. et al. Immunotherapy with autologous dendritic cells in the complex treatment of malignant gliomas - results. J Neurooncol 166, 309–319 (2024). https://doi.org/10.1007/s11060-023-04559-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-023-04559-1

Keywords

Search

Navigation