Immune system dysfunction in patients with glioblastoma. Literature review. Clinical cases
S. S. Sklyar,
D. A. Sitovskaya,
Iu. V. Mirolyubova,
V. S. Kushnirova,
B. I. Safarov,
K. A. Samochernykh https://doi.org/10.56618/2071-2693_2023_15_4_200
EDN: DQANHH
Abstract
The first attempts to use immunotherapy in the treatment of patients with glioblastoma were not successful enough. This failure was associated with the immunological privilege of the brain, such features of the tumor itself as low mutational load and genetic heterogeneity. Research conducted in recent years has clarified the features of the functioning of the immune system in the patients with glioblastoma. Today, one of the leading factors of immunosuppression is systemic lymphopenia, not only of an iatrogenic nature, but also induced by the tumor itself. We have presented a review on this topic with a description of three clinical cases with an assessment of the lymphocyte subpopulation in the peripheral blood and the infiltration of immune system cells into the tumor. Immunotherapy options for this group of patients are also presented, taking into account the particularities of the functioning of the immune system.
About the Authors
S. S. Sklyar
Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Sofia S. Sklyar.
12, Mayakovskogo st., St. Petersburg, 191014
D. A. Sitovskaya
Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Daria A. Sitovskaya.
12, Mayakovskogo st., St. Petersburg, 191014
Iu. V. Mirolyubova
Almazov National Medical Research Centre
Russian Federation
Russian Federation
Iulia V. Mirolyubova.
2, Akkгratova st., St. petersburg, 197341
V. S. Kushnirova
Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Victoria S. Kushnirova.
12, Mayakovskogo st., St. Petersburg, 191014
B. I. Safarov
Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Bobir I. Safarov.
12, Mayakovskogo st., St. Petersburg, 191014
K. A. Samochernykh
Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Konstantin A. Samochernykh.
12, Mayakovskogo st., St. Petersburg, 191014
References
1. Abbot M., Ustoyev Y. Cancer and the Immune System: The History and Background of Immunotherapy. Semin Oncol Nurs. 2019;35(5):150923. doi: 10.1016/j.soncn.2019.08.002.
2. Blair G. E., Cook G. p. Cancer and the immune system: an overview. Oncogene. 2008;27(45):5868. doi: 10.1038/onc.2008.277.
3. Dunn G. P., Old L. J., Schreiber R. D. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60. doi: 10.1146/annurev.immunol.22.012703.104803.
4. Chen d. S., Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10. doi: 10.1016/j.immuni.2013.07.012.
5. Topalian S., Hodi F. S., Brahmer J. R., Gettinger S. N., Smith D. C., Mcdermott D.F., Powderly J. D., Carvajal R. D., Sosman J.A., Atkins M. B., Leming P. D., Spigel D. R., Antonia S. J., Horn L., Drake C. G., Pardoll D. M., Chen L., Sharfman W. H., Anders R.A., Taube J. M., Mcmiller T.L., Xu H., Korman A. J., Jure-Kunkel M., Sznol M. Safety, activity, and immune correlates of anti-pd-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54. doi:10.1056/NEJMoa1200690.
6. Sklyar S. S., Trashkov A. P., Matsko M. V., Safarov B. I., Vasiliev A. G. Immune response to primary glioblastoma. pediatrician. 2022;13(2):49–60. (In Russ.). doi: 10.17816/PED13249–60.
7. Aspelund A., Antila S., Proulx S. T., Karlsen T. V., Karaman S., Detmar M., Wiig H., Alitalo K. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 2015;212:991–999. doi: 10.1084/jem.20142290.
8. Louveau A., Smirnov I., Keyes T. J., Eccles J. D., Rouhani S. J., Peske J. D., Derecki N. C., Castle D., Mandell J. W., Lee K. S. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523:337–341. doi: 10.1038/nature14432.
9. Majc B., Novak M., Kopitar-Jerala N., Jewett A., Breznik B. Immunotherapy of Glioblastoma: Current Strategies and Challenges in Tumor Model development. Cells. 2021;10(265):2–22. doi: 10.3390/cells10020265.
10. Kondratyev A. N., Tsentsiper L. M. Glymphatic system of the brain: structure and practical significance. Russian Journal of Anaesthesiology and Reanimatology. Anesteziologiya i Reanimatologiya. 2019;6:72–80. (In Russ.). doi: 10.17116/anaesthesiology201906172.
11. Brat D. J., Ellison D. W., Figarella-Branger D., Hawkins C. E., Louis D. N. et al. WHO Classification of Tumours Editorial Board. Central nervous system tumours. Lyon (France): International Agency for Research on Cancer. WHO Classification of Tumours Series, 5th ed.; 2021; vol. 2.
12. Ostom Q.T., Price M., Neff C., Cioffi G., Waite K.A., Kruchko C., Barnholtz-Sloan J.S. CBTRUS Statistical Report: primary Brain and Other Central Nervous System Tumors diagnosed in the United States in 2015–2019. Neuro Oncol. 2022;24:1–95. doi: 10.1093/neuonc/noac202.
13. Matsko M. V., Sklyar S. S., Ulitin A. Yu., Matsko D. E., Imyanitov E. N., Ievleva A. G., Ni V. I., Volkov N. M., Zrelov A. A., Baksheeva A. O., Galkina D. V. Changes in the MGMT gene expression in patients with primary glioblastoma after relapse. Influence of clinical characteristics and MGMT expression on survival of patients. Siberian Journal of Oncology. 2021;20(3): 5–17. (In Russ.). doi: 10.21294/1814-4861-2021-20-3–5–17.
14. Nechaeva A. S., Kukanov K. K. Achievements and prospects in dendritic cell vaccine therapy in patients with malignant glial tumors. Russian Journal for Personalized Medicine. 2023;3(3):79–90. (In Russ.) doi: 10.18705/2782-3806-2023-3-3–79–90.
15. Nazaralieva E.T., Fedorov V. S., Zabrodskaya Yu.M., Kim A.V., Djanaliev B. R., Shevtsov M.A., Samochernych K. A. Heat shock proteins as diagnostic and prognostic markers in malignant tumors of the central nervous system. Translational Medicine. 2022;9(6):5–15. (In Russ.) doi: 10.18705/2311-4495-2022-9-6–5–15.
16. Filley A. C., Henriquez M., Dey M. Recurrent glioma clinical trial, checkmate-143: the game is not over yet. Oncotarget. 2017;8(53):91779–91794. doi: 10.18632/oncotarget.21586.
17. Omuro A., Vlahovic G., Lim M., Sahebjam S., Baehring J., Cloughesy T. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase 1 cohorts of checkmate 143. Neuro-Oncology. 2018;20(5):674–686. doi: 10.1093/neuonc/nox208.
18. Jackson C. M., Choi J., Lim M. Mechanisms of immunotherapy resistance: lessons from glioblastoma. Nature Immunology. 2019;20(9):1100–1109. doi: 10.1038/s41590–019–0433-y.
19. Berghoff A. S., Kiesel B., Widhalm G., Rajky O., Ricken G., Wohrer A. programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro-Oncology. 2015;17:1064–1075. doi: 10.1093/neuonc/nou307.
20. Nduom E. K., Wei J., Yaghi N. K., Huang N., Kong L. Y., Gabrusiewicz K. PD-L1 expression and prognostic impact in glioblastoma. Neuro-Oncology. 2016; 18(2):195–205. doi: 10.1093/neuonc/nov172.
21. Laviron M., Boissonnas A. Ontogeny of Tumor-Associated macrophages. Frontiers in Immunology. Front Immunol. 2019;31;10:1799. doi: 10.3389/fimmu.2019.01799.
22. Majc B., Novak M., Kopitar-Jerala N., Jewett A., Breznik B. Immunotherapy of Glioblastoma: Current Strategies and Challenges in Tumor Model development. Cells. 2021;10(265):2–22. doi: 10.3390/cells10020265.
23. Li F., Li C., Cai X., Xie Z., Zhou L., Chaeng B., Zhong R., Xiong S., Li J., Chen Z., Yu Z., He J., Liang W. The association between Cd 8+ tumor-infiltrating lymphocytes and the clinical outcome of cancer immunotherapy: A systematic review and meta-analysis. EClinicalMedicine. 2021;41:101134. doi: 10.1016/j.eclinm.2021.101134.
24. Chetveryakov A. V., Tereshkov P. P., Tsepelev V. L., Kryukova V. V. Cytotoxic T-lymphocyte subpopulations content in patients with colon tumor. Modern problems of Science and Education. 2023;3. (In Russ.) doi: 10.17513/spno.32682.
25. Jin K., Cao Y., Gu Y. poor clinical outcomes and immunoevasive contexture in CXCL13+CD 8+ T-cells enriched gastric cancer patients. Oncoimmunology. 2021;10 (1):1915560. doi: 10.1080/2162402X.2021.1915560.
26. Radpour R., Riether C., Simillion C. CD8+ T cells expand stem and progenitor cells in favorable but not adverse risk acute myeloid leukemia. Leukemia. 2019;33(10):2379–2392. doi: 10.1038/s41375-019-0441-9.
27. Wang W. J. Variation of blood T lymphocyte subgroups in patients with non-small cell lung cancer. Asian pacific journal of cancer prevention. 2013;14(8): 4671–4673. doi: 10.7314/APJCP.2013.14.8.4671.
28. Semiglazov V. F., Tseluiko A. I., Baldueva I.A., Nekhaeva T. L., Artemyeva A. S., Kudaybergenova A. G., Protsenko S.A., Novik A.V., Semiglazov V.V., Donskikh R.V., Semiglazova T. Yu., Pesotskiy R. S., Apollonova V. S., Krivorotko P. V., Belyaev A. M. Immunology and immunotherapy in the complex treatment of malignant tumors. Meditsinskiy sovet. Medical Council. 2021;(4):248–257. (In Russ.) doi: 10.21518/2079–701X-2021–4–248–257.
29. Mahaley M. S. Jr., Brooks w. H., Roszman T. L. (1977) Immunobiology of primary intracranial tumors. part 1: studies of the cellular and humoral general immune competence of brain-tumor patients. J Neurosurg. 1977; 46:467–476. doi: 10.3171/jns.1977.46.4.0467.
30. Dix A. R., Brooks W. H., Roszman T. L. Immune defects observed in patients with primary malignant brain tumors. J Neuroimmunol. 1999;100:216–232. doi: 10.1016/S0165–5728(99)00203-9.
31. Woroniecka K. I., Rhodin K. E., Chongsathidkiet P. T-cell dysfunction in Glioblastoma: applying a new framework. Clin Cancer Res. 2018;24(16):3792–3802. doi: 10.1158/1078–0432.CCR-18–0047.
32. Kim W. J., Dho Y., Ock C., Kim J. W., Choi S. H., Lee S., Kim I. H., Kim T. M., Park C. K. Clinical observation of lymphopenia in patients with newly diagnosed glioblastoma. J Neurooncol. 2019;143(2):321–328. doi: 10.1007/s11060-019-03167-2.
33. Chongsathidkiet P., Jackson C., Koyama S., Loebel F., Cui X., Farber S. H., Woroniecka K., Elsamadicy A., Dechant C. A., Kemery H. R., Sanchez-Perez L., Cheema T.A. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med. 2018;24(9):1459–1468. doi: 10.1038/s41591-018-0135-2.
34. Iorgulescu J. B., Gokhale P. C., Speranza M. C., Eschle B. K., Poitras M. J., Wilkens M. K., Soroko K. M. Concurrent dexamethasone Limits the Clinical Benefit of Immune Checkpoint Blockade in Glioblastoma. Clin Cancer Res. 2021;27(1):276–287. doi: 10.1158/1078–0432.CCR-20–2291.
35. Giles A., Hutchinson M. N.D., Sonnemann H. M., Jung J., Fecci P. E. dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer. 2018;6(1):51. doi: 10.1186/s40425-018-0371-5.
36. Karachi A., Dastmalchi F., Mitchell D.A., Rahman M. Temozolomide for immunomodulation in the treatment of glioblastoma. Neuro Oncol. 2018;20(12):1566–1572. doi: 10.1093/neuonc/noy072.
37. Hotchkiss K. M., Sampson J. H. Temozolomide treatment outcomes and immunotherapy efficacy in brain tumor. J Neurooncol. 2021;151(1):55–62. doi: 10.1007/s11060-020-03598-2.
38. Yu M.W., Quail D. F. Immunotherapy for Glioblastoma: Current progress and Challenges. Front Immunol. 2021:12:676301. doi: 10.3389/fimmu.2021.676301.
Review
For citations:
Sklyar S.S., Sitovskaya D.A., Mirolyubova I.V., Kushnirova V.S., Safarov B.I., Samochernykh K.A. Immune system dysfunction in patients with glioblastoma. Literature review. Clinical cases. Russian Neurosurgical Journal named after Professor A. L. Polenov. 2023;15(4):200-208. (In Russ.) https://doi.org/10.56618/2071-2693_2023_15_4_200. EDN: DQANHH
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