Skip to main content
Top

26-03-2024 | Glioblastoma | REVIEW

Glioblastoma stem cell metabolism and immunity

Published in: Cancer and Metastasis Reviews

Login to get access

Abstract

Despite enormous efforts being invested in the development of novel therapies for brain malignancies, there remains a dire need for effective treatments, particularly for pediatric glioblastomas. Their poor prognosis has been attributed to the fact that conventional therapies target tumoral cells, but not glioblastoma stem cells (GSCs). GSCs are characterized by self-renewal, tumorigenicity, poor differentiation, and resistance to therapy. These characteristics represent the fundamental tools needed to recapitulate the tumor and result in a relapse. The mechanisms by which GSCs alter metabolic cues and escape elimination by immune cells are discussed in this article, along with potential strategies to harness effector immune cells against GSCs. As cellular immunotherapy is making significant advances in a variety of cancers, leveraging this underexplored reservoir may result in significant improvements in the treatment options for brain malignancies.
Literature
1.
go back to reference Alvarado, A. G., Thiagarajan, P. S., Mulkearns-Hubert, E. E., Silver, D. J., Hale, J. S., Alban, T. J., … Lathia, J. D. (2017). Glioblastoma cancer stem cells evade innate immune suppression of self-renewal through reduced TLR4 expression. Cell Stem Cell, 20(4), 450–461.e4. https://doi.org/10.1016/j.stem.2016.12.001 Alvarado, A. G., Thiagarajan, P. S., Mulkearns-Hubert, E. E., Silver, D. J., Hale, J. S., Alban, T. J., … Lathia, J. D. (2017). Glioblastoma cancer stem cells evade innate immune suppression of self-renewal through reduced TLR4 expression. Cell Stem Cell, 20(4), 450–461.e4. https://​doi.​org/​10.​1016/​j.​stem.​2016.​12.​001
10.
go back to reference Lahkola, A., Auvinen, A., Raitanen, J., Schoemaker, M. J., Christensen, H. C., Feychting, M., … Salminen, T. (2007). Mobile phone use and risk of glioma in 5 North European countries. International Journal of Cancer, 120(8), 1769–1775. https://doi.org/10.1002/ijc.22503 Lahkola, A., Auvinen, A., Raitanen, J., Schoemaker, M. J., Christensen, H. C., Feychting, M., … Salminen, T. (2007). Mobile phone use and risk of glioma in 5 North European countries. International Journal of Cancer, 120(8), 1769–1775. https://​doi.​org/​10.​1002/​ijc.​22503
14.
18.
go back to reference Ostrom, Q. T., Cioffi, G., Waite, K., Kruchko, C., & Barnholtz-Sloan, J. S. (2021). CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2014–2018. Neuro-Oncology, 23(12 Suppl 2), iii1–iii105. https://doi.org/10.1093/neuonc/noab200 Ostrom, Q. T., Cioffi, G., Waite, K., Kruchko, C., & Barnholtz-Sloan, J. S. (2021). CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2014–2018. Neuro-Oncology, 23(12 Suppl 2), iii1–iii105. https://​doi.​org/​10.​1093/​neuonc/​noab200
25.
go back to reference Ozawa, M., Brennan, P. M., Zienius, K., Kurian, K. M., Hollingworth, W., Weller, D., … Ben-Shlomo, Y. (2019). The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour: A case-control study using the clinical practice research database (CPRD) (2000–2014). BMJ Open, 9(8), e029686. https://doi.org/10.1136/bmjopen-2019-029686 Ozawa, M., Brennan, P. M., Zienius, K., Kurian, K. M., Hollingworth, W., Weller, D., … Ben-Shlomo, Y. (2019). The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour: A case-control study using the clinical practice research database (CPRD) (2000–2014). BMJ Open, 9(8), e029686. https://​doi.​org/​10.​1136/​bmjopen-2019-029686
27.
go back to reference Verburg, N., Hoefnagels, F. W. A., Barkhof, F., Boellaard, R., Goldman, S., Guo, J., … De Witt Hamer, P. C. (2017). Diagnostic accuracy of neuroimaging to delineate diffuse gliomas within the brain: A meta-analysis. AJNR: American Journal of Neuroradiology, 38(10), 1884–1891. https://doi.org/10.3174/ajnr.A5368 Verburg, N., Hoefnagels, F. W. A., Barkhof, F., Boellaard, R., Goldman, S., Guo, J., … De Witt Hamer, P. C. (2017). Diagnostic accuracy of neuroimaging to delineate diffuse gliomas within the brain: A meta-analysis. AJNR: American Journal of Neuroradiology, 38(10), 1884–1891. https://​doi.​org/​10.​3174/​ajnr.​A5368
28.
go back to reference Wen, P. Y., Macdonald, D. R., Reardon, D. A., Cloughesy, T. F., Sorensen, A. G., Galanis, E., … Chang, S. M. (2010). Updated response assessment criteria for high-grade gliomas: Response assessment in neuro-oncology working group. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 28(11), 1963–1972. https://doi.org/10.1200/JCO.2009.26.3541 Wen, P. Y., Macdonald, D. R., Reardon, D. A., Cloughesy, T. F., Sorensen, A. G., Galanis, E., … Chang, S. M. (2010). Updated response assessment criteria for high-grade gliomas: Response assessment in neuro-oncology working group. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 28(11), 1963–1972. https://​doi.​org/​10.​1200/​JCO.​2009.​26.​3541
29.
go back to reference van den Bent, M. J., Wefel, J. S., Schiff, D., Taphoorn, M. J. B., Jaeckle, K., Junck, L., … Jacobs, A. H. (2011). Response assessment in neuro-oncology (a report of the RANO group): Assessment of outcome in trials of diffuse low-grade gliomas. The Lancet. Oncology, 12(6), 583–593. https://doi.org/10.1016/S1470-2045(11)70057-2 van den Bent, M. J., Wefel, J. S., Schiff, D., Taphoorn, M. J. B., Jaeckle, K., Junck, L., … Jacobs, A. H. (2011). Response assessment in neuro-oncology (a report of the RANO group): Assessment of outcome in trials of diffuse low-grade gliomas. The Lancet. Oncology, 12(6), 583–593. https://​doi.​org/​10.​1016/​S1470-2045(11)70057-2
31.
go back to reference Cohen, K. J., Pollack, I. F., Zhou, T., Buxton, A., Holmes, E. J., Burger, P. C., … Heideman, R. L. (2011). Temozolomide in the treatment of high-grade gliomas in children: A report from the Children’s Oncology Group. Neuro-Oncology, 13(3), 317–323. https://doi.org/10.1093/neuonc/noq191 Cohen, K. J., Pollack, I. F., Zhou, T., Buxton, A., Holmes, E. J., Burger, P. C., … Heideman, R. L. (2011). Temozolomide in the treatment of high-grade gliomas in children: A report from the Children’s Oncology Group. Neuro-Oncology, 13(3), 317–323. https://​doi.​org/​10.​1093/​neuonc/​noq191
37.
go back to reference Milde, T., Kleber, S., Korshunov, A., Witt, H., Hielscher, T., Koch, P., … Witt, O. (2011). A novel human high-risk ependymoma stem cell model reveals the differentiation-inducing potential of the histone deacetylase inhibitor Vorinostat. Acta Neuropathologica, 122(5), 637–650. https://doi.org/10.1007/s00401-011-0866-3 Milde, T., Kleber, S., Korshunov, A., Witt, H., Hielscher, T., Koch, P., … Witt, O. (2011). A novel human high-risk ependymoma stem cell model reveals the differentiation-inducing potential of the histone deacetylase inhibitor Vorinostat. Acta Neuropathologica, 122(5), 637–650. https://​doi.​org/​10.​1007/​s00401-011-0866-3
39.
go back to reference Sun, Y., Xu, C., Pan, C., Chen, X., Geng, Y., Wu, Y., … Zhang, L. (2019). Diffuse intrinsic pontine gliomas exhibit cell biological and molecular signatures of fetal hindbrain-derived neural progenitor cells. Neuroscience Bulletin, 35(2), 216–224. https://doi.org/10.1007/s12264-018-00329-6 Sun, Y., Xu, C., Pan, C., Chen, X., Geng, Y., Wu, Y., … Zhang, L. (2019). Diffuse intrinsic pontine gliomas exhibit cell biological and molecular signatures of fetal hindbrain-derived neural progenitor cells. Neuroscience Bulletin, 35(2), 216–224. https://​doi.​org/​10.​1007/​s12264-018-00329-6
40.
go back to reference Filbin, M. G., Tirosh, I., Hovestadt, V., Shaw, M. L., Escalante, L. E., Mathewson, N. D., … Suvà, M. L. (2018). Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science, 360(6386), 331–335. https://doi.org/10.1126/science.aao4750 Filbin, M. G., Tirosh, I., Hovestadt, V., Shaw, M. L., Escalante, L. E., Mathewson, N. D., … Suvà, M. L. (2018). Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science, 360(6386), 331–335. https://​doi.​org/​10.​1126/​science.​aao4750
45.
go back to reference Lombard, A., Digregorio, M., Delcamp, C., Rogister, B., Piette, C., & Coppieters, N. (2021). The subventricular zone, a hideout for adult and pediatric high-grade glioma stem cells. Frontiers in Oncology, 10. Retrieved from https://www.frontiersin.org/articles/https://doi.org/10.3389/fonc.2020.614930 Lombard, A., Digregorio, M., Delcamp, C., Rogister, B., Piette, C., & Coppieters, N. (2021). The subventricular zone, a hideout for adult and pediatric high-grade glioma stem cells. Frontiers in Oncology, 10. Retrieved from https://​www.​frontiersin.​org/​articles/​https://​doi.​org/​10.​3389/​fonc.​2020.​614930
47.
go back to reference Genadry, K. C., Pietrobono, S., Rota, R., & Linardic, C. M. (2018). Soft tissue sarcoma cancer stem cells: An overview. Frontiers in Oncology, 8. Retrieved from https://www.frontiersin.org/articles/https://doi.org/10.3389/fonc.2018.00475 Genadry, K. C., Pietrobono, S., Rota, R., & Linardic, C. M. (2018). Soft tissue sarcoma cancer stem cells: An overview. Frontiers in Oncology, 8. Retrieved from https://​www.​frontiersin.​org/​articles/​https://​doi.​org/​10.​3389/​fonc.​2018.​00475
52.
53.
go back to reference Singh, S. K., Clarke, I. D., Terasaki, M., Bonn, V. E., Hawkins, C., Squire, J., & Dirks, P. B. (2003). Identification of a cancer stem cell in human brain tumors. Cancer Research, 63(18), 5821–5828.PubMed Singh, S. K., Clarke, I. D., Terasaki, M., Bonn, V. E., Hawkins, C., Squire, J., & Dirks, P. B. (2003). Identification of a cancer stem cell in human brain tumors. Cancer Research, 63(18), 5821–5828.PubMed
56.
57.
62.
go back to reference Pearson, J. R. D., Cuzzubbo, S., McArthur, S., Durrant, L. G., Adhikaree, J., Tinsley, C. J., … McArdle, S. E. B. (2020). Immune escape in glioblastoma multiforme and the adaptation of immunotherapies for treatment. Frontiers in Immunology, 11, 582106. https://doi.org/10.3389/fimmu.2020.582106 Pearson, J. R. D., Cuzzubbo, S., McArthur, S., Durrant, L. G., Adhikaree, J., Tinsley, C. J., … McArdle, S. E. B. (2020). Immune escape in glioblastoma multiforme and the adaptation of immunotherapies for treatment. Frontiers in Immunology, 11, 582106. https://​doi.​org/​10.​3389/​fimmu.​2020.​582106
63.
go back to reference Gravina, G. L., Colapietro, A., Mancini, A., Rossetti, A., Martellucci, S., Ventura, L., … Festuccia, C. (2022). ATX-101, a peptide targeting PCNA, has antitumor efficacy alone or in combination with radiotherapy in murine models of human glioblastoma. Cancers, 14(2), 289. https://doi.org/10.3390/cancers14020289 Gravina, G. L., Colapietro, A., Mancini, A., Rossetti, A., Martellucci, S., Ventura, L., … Festuccia, C. (2022). ATX-101, a peptide targeting PCNA, has antitumor efficacy alone or in combination with radiotherapy in murine models of human glioblastoma. Cancers, 14(2), 289. https://​doi.​org/​10.​3390/​cancers14020289
68.
go back to reference Mitsutake, Y., Hiromatsu, Y., Saisho, M., Tokunaga, N., Ichikawa, Y., Kaji, M., & Irie, K. (1986). [Immunological assay of the CA-125 value in pleural effusion in various types of pleuritis--Its application as a differential diagnostic parameter of tuberculous or carcinomatous pleuritis]. Gan No Rinsho. Japan Journal of Cancer Clinics, 32(5), 453–457. Mitsutake, Y., Hiromatsu, Y., Saisho, M., Tokunaga, N., Ichikawa, Y., Kaji, M., & Irie, K. (1986). [Immunological assay of the CA-125 value in pleural effusion in various types of pleuritis--Its application as a differential diagnostic parameter of tuberculous or carcinomatous pleuritis]. Gan No Rinsho. Japan Journal of Cancer Clinics, 32(5), 453–457.
71.
go back to reference Enderlin, M., Kleinmann, E. V., Struyf, S., Buracchi, C., Vecchi, A., Kinscherf, R., … Dinsart, C. (2009). TNF-alpha and the IFN-gamma-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma. Cancer Gene Therapy, 16(2), 149–160. https://doi.org/10.1038/cgt.2008.62 Enderlin, M., Kleinmann, E. V., Struyf, S., Buracchi, C., Vecchi, A., Kinscherf, R., … Dinsart, C. (2009). TNF-alpha and the IFN-gamma-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma. Cancer Gene Therapy, 16(2), 149–160. https://​doi.​org/​10.​1038/​cgt.​2008.​62
72.
73.
go back to reference Ruggeri, L., Capanni, M., Urbani, E., Perruccio, K., Shlomchik, W. D., Tosti, A., … Velardi, A. (2002). Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science (New York, N.Y.), 295(5562), 2097–2100. https://doi.org/10.1126/science.1068440 Ruggeri, L., Capanni, M., Urbani, E., Perruccio, K., Shlomchik, W. D., Tosti, A., … Velardi, A. (2002). Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science (New York, N.Y.), 295(5562), 2097–2100. https://​doi.​org/​10.​1126/​science.​1068440
74.
go back to reference Kim, H., Kim, J., Sa, J. K., Ryu, B.-K., Park, K.-J., Kim, J., … Kang, S.-H. (2022). Calcipotriol, a synthetic Vitamin D analog, promotes antitumor immunity via CD4+T-dependent CTL/NK cell activation. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 154, 113553. https://doi.org/10.1016/j.biopha.2022.113553 Kim, H., Kim, J., Sa, J. K., Ryu, B.-K., Park, K.-J., Kim, J., … Kang, S.-H. (2022). Calcipotriol, a synthetic Vitamin D analog, promotes antitumor immunity via CD4+T-dependent CTL/NK cell activation. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 154, 113553. https://​doi.​org/​10.​1016/​j.​biopha.​2022.​113553
75.
go back to reference Salazar, N., Carlson, J. C., Huang, K., Zheng, Y., Oderup, C., Gross, J., … Zabel, B. A. (2018). A chimeric antibody against ACKR3/CXCR7 in combination with TMZ activates immune responses and extends survival in mouse GBM models. Molecular Therapy: The Journal of the American Society of Gene Therapy, 26(5), 1354–1365. https://doi.org/10.1016/j.ymthe.2018.02.030 Salazar, N., Carlson, J. C., Huang, K., Zheng, Y., Oderup, C., Gross, J., … Zabel, B. A. (2018). A chimeric antibody against ACKR3/CXCR7 in combination with TMZ activates immune responses and extends survival in mouse GBM models. Molecular Therapy: The Journal of the American Society of Gene Therapy, 26(5), 1354–1365. https://​doi.​org/​10.​1016/​j.​ymthe.​2018.​02.​030
80.
go back to reference Pombo Antunes, A. R., Scheyltjens, I., Duerinck, J., Neyns, B., Movahedi, K., & Van Ginderachter, J. A. (2020). Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies. eLife, 9, e52176. https://doi.org/10.7554/eLife.52176 Pombo Antunes, A. R., Scheyltjens, I., Duerinck, J., Neyns, B., Movahedi, K., & Van Ginderachter, J. A. (2020). Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies. eLife, 9, e52176. https://​doi.​org/​10.​7554/​eLife.​52176
86.
go back to reference van Hooren, L., Handgraaf, S. M., Kloosterman, D. J., Karimi, E., van Mil, L. W. H. G., Gassama, A. A., … Akkari, L. (2023). CD103+ regulatory T cells underlie resistance to radio-immunotherapy and impair CD8+ T cell activation in glioblastoma. Nature Cancer, 4(5), 665–681. https://doi.org/10.1038/s43018-023-00547-6 van Hooren, L., Handgraaf, S. M., Kloosterman, D. J., Karimi, E., van Mil, L. W. H. G., Gassama, A. A., … Akkari, L. (2023). CD103+ regulatory T cells underlie resistance to radio-immunotherapy and impair CD8+ T cell activation in glioblastoma. Nature Cancer, 4(5), 665–681. https://​doi.​org/​10.​1038/​s43018-023-00547-6
87.
go back to reference Yoshioka, S., Ikeda, T., Fukuchi, S., Kawai, Y., Ohta, K., Murakami, H., … Asai, A. (2022). Identification and characterization of a novel dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase. International journal of tryptophan research: IJTR, 15, 11786469221138456. https://doi.org/10.1177/11786469221138456 Yoshioka, S., Ikeda, T., Fukuchi, S., Kawai, Y., Ohta, K., Murakami, H., … Asai, A. (2022). Identification and characterization of a novel dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase. International journal of tryptophan research: IJTR, 15, 11786469221138456. https://​doi.​org/​10.​1177/​1178646922113845​6
89.
91.
go back to reference Griesinger, A. M., Birks, D. K., Donson, A. M., Amani, V., Hoffman, L. M., Waziri, A., … Foreman, N. K. (2013). Characterization of distinct immunophenotypes across pediatric brain tumor types. Journal of Immunology (Baltimore, Md.: 1950), 191(9), 4880–4888. https://doi.org/10.4049/jimmunol.1301966 Griesinger, A. M., Birks, D. K., Donson, A. M., Amani, V., Hoffman, L. M., Waziri, A., … Foreman, N. K. (2013). Characterization of distinct immunophenotypes across pediatric brain tumor types. Journal of Immunology (Baltimore, Md.: 1950), 191(9), 4880–4888. https://​doi.​org/​10.​4049/​jimmunol.​1301966
93.
go back to reference Lieberman, N. A. P., DeGolier, K., Kovar, H. M., Davis, A., Hoglund, V., Stevens, J., … Crane, C. A. (2019). Characterization of the immune microenvironment of diffuse intrinsic pontine glioma: Implications for development of immunotherapy. Neuro-Oncology, 21(1), 83–94. https://doi.org/10.1093/neuonc/noy145 Lieberman, N. A. P., DeGolier, K., Kovar, H. M., Davis, A., Hoglund, V., Stevens, J., … Crane, C. A. (2019). Characterization of the immune microenvironment of diffuse intrinsic pontine glioma: Implications for development of immunotherapy. Neuro-Oncology, 21(1), 83–94. https://​doi.​org/​10.​1093/​neuonc/​noy145
98.
101.
102.
go back to reference Goidts, V., Bageritz, J., Puccio, L., Nakata, S., Zapatka, M., Barbus, S., … Radlwimmer, B. (2012). RNAi screening in glioma stem-like cells identifies PFKFB4 as a key molecule important for cancer cell survival. Oncogene, 31(27), 3235–3243. https://doi.org/10.1038/onc.2011.490 Goidts, V., Bageritz, J., Puccio, L., Nakata, S., Zapatka, M., Barbus, S., … Radlwimmer, B. (2012). RNAi screening in glioma stem-like cells identifies PFKFB4 as a key molecule important for cancer cell survival. Oncogene, 31(27), 3235–3243. https://​doi.​org/​10.​1038/​onc.​2011.​490
103.
go back to reference Ye, X.-Q., Li, Q., Wang, G.-H., Sun, F.-F., Huang, G.-J., Bian, X.-W., … Qian, G.-S. (2011). Mitochondrial and energy metabolism-related properties as novel indicators of lung cancer stem cells. International Journal of Cancer, 129(4), 820–831. https://doi.org/10.1002/ijc.25944 Ye, X.-Q., Li, Q., Wang, G.-H., Sun, F.-F., Huang, G.-J., Bian, X.-W., … Qian, G.-S. (2011). Mitochondrial and energy metabolism-related properties as novel indicators of lung cancer stem cells. International Journal of Cancer, 129(4), 820–831. https://​doi.​org/​10.​1002/​ijc.​25944
105.
go back to reference Sriramkumar, S., Sood, R., Huntington, T. D., Ghobashi, A. H., Vuong, T. T., Metcalfe, T. X., … O’Hagan, H. M. (2022). Platinum-induced mitochondrial OXPHOS contributes to cancer stem cell enrichment in ovarian cancer. Journal of Translational Medicine, 20(1), 246. https://doi.org/10.1186/s12967-022-03447-y Sriramkumar, S., Sood, R., Huntington, T. D., Ghobashi, A. H., Vuong, T. T., Metcalfe, T. X., … O’Hagan, H. M. (2022). Platinum-induced mitochondrial OXPHOS contributes to cancer stem cell enrichment in ovarian cancer. Journal of Translational Medicine, 20(1), 246. https://​doi.​org/​10.​1186/​s12967-022-03447-y
106.
go back to reference Janiszewska, M., Suvà, M. L., Riggi, N., Houtkooper, R. H., Auwerx, J., Clément-Schatlo, V., … Stamenkovic, I. (2012). Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells. Genes & Development, 26(17), 1926–1944. https://doi.org/10.1101/gad.188292.112 Janiszewska, M., Suvà, M. L., Riggi, N., Houtkooper, R. H., Auwerx, J., Clément-Schatlo, V., … Stamenkovic, I. (2012). Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells. Genes & Development, 26(17), 1926–1944. https://​doi.​org/​10.​1101/​gad.​188292.​112
108.
go back to reference Vlashi, E., Lagadec, C., Vergnes, L., Matsutani, T., Masui, K., Poulou, M., … Pajonk, F. (2011). Metabolic state of glioma stem cells and nontumorigenic cells. Proceedings of the National Academy of Sciences, 108(38), 16062–16067. https://doi.org/10.1073/pnas.1106704108 Vlashi, E., Lagadec, C., Vergnes, L., Matsutani, T., Masui, K., Poulou, M., … Pajonk, F. (2011). Metabolic state of glioma stem cells and nontumorigenic cells. Proceedings of the National Academy of Sciences, 108(38), 16062–16067. https://​doi.​org/​10.​1073/​pnas.​1106704108
118.
go back to reference Ju, J.-M., Nam, G., Lee, Y.-K., Jung, M., Chang, H., Kim, W., … Choi, E. Y. (2021). IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease. Proceedings of the National Academy of Sciences, 118(10), e2011170118. https://doi.org/10.1073/pnas.2011170118 Ju, J.-M., Nam, G., Lee, Y.-K., Jung, M., Chang, H., Kim, W., … Choi, E. Y. (2021). IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease. Proceedings of the National Academy of Sciences, 118(10), e2011170118. https://​doi.​org/​10.​1073/​pnas.​2011170118
122.
go back to reference Liu, C., Chikina, M., Deshpande, R., Menk, A. V., Wang, T., Tabib, T., … Vignali, D. A. A. (2019). Treg cells promote the SREBP1-dependent metabolic fitness of tumor-promoting macrophages via repression of CD8+ T cell-derived interferon-γ. Immunity, 51(2), 381–397.e6. https://doi.org/10.1016/j.immuni.2019.06.017 Liu, C., Chikina, M., Deshpande, R., Menk, A. V., Wang, T., Tabib, T., … Vignali, D. A. A. (2019). Treg cells promote the SREBP1-dependent metabolic fitness of tumor-promoting macrophages via repression of CD8+ T cell-derived interferon-γ. Immunity, 51(2), 381–397.e6. https://​doi.​org/​10.​1016/​j.​immuni.​2019.​06.​017
128.
go back to reference Surowiec, R. K., Ferris, S. F., Apfelbaum, A., Espinoza, C., Mehta, R. K., Monchamp, K., … Galban, S. (2021). Transcriptomic analysis of diffuse intrinsic pontine glioma (DIPG) identifies a targetable ALDH-positive subset of highly tumorigenic cancer stem-like cells. Molecular Cancer Research, 19(2), 223–239. https://doi.org/10.1158/1541-7786.MCR-20-0464 Surowiec, R. K., Ferris, S. F., Apfelbaum, A., Espinoza, C., Mehta, R. K., Monchamp, K., … Galban, S. (2021). Transcriptomic analysis of diffuse intrinsic pontine glioma (DIPG) identifies a targetable ALDH-positive subset of highly tumorigenic cancer stem-like cells. Molecular Cancer Research, 19(2), 223–239. https://​doi.​org/​10.​1158/​1541-7786.​MCR-20-0464
129.
go back to reference Murakami, T., Nakazawa, T., Natsume, A., Nishimura, F., Nakamura, M., Matsuda, R., … Nakase, H. (2018). Novel human NK cell line carrying CAR targeting EGFRvIII induces antitumor effects in glioblastoma cells. Anticancer Research, 38(9), 5049–5056. https://doi.org/10.21873/anticanres.12824 Murakami, T., Nakazawa, T., Natsume, A., Nishimura, F., Nakamura, M., Matsuda, R., … Nakase, H. (2018). Novel human NK cell line carrying CAR targeting EGFRvIII induces antitumor effects in glioblastoma cells. Anticancer Research, 38(9), 5049–5056. https://​doi.​org/​10.​21873/​anticanres.​12824
131.
go back to reference Sönmez, C., Wölfer, J., Holling, M., Brokinkel, B., Stummer, W., Wiendl, H., … Grauer, O. M. (2022). Blockade of inhibitory killer cell immunoglobulin-like receptors and IL-2 triggering reverses the functional hypoactivity of tumor-derived NK-cells in glioblastomas. Scientific Reports, 12(1), 6769. https://doi.org/10.1038/s41598-022-10680-4 Sönmez, C., Wölfer, J., Holling, M., Brokinkel, B., Stummer, W., Wiendl, H., … Grauer, O. M. (2022). Blockade of inhibitory killer cell immunoglobulin-like receptors and IL-2 triggering reverses the functional hypoactivity of tumor-derived NK-cells in glioblastomas. Scientific Reports, 12(1), 6769. https://​doi.​org/​10.​1038/​s41598-022-10680-4
132.
go back to reference Weiss, T., Schneider, H., Silginer, M., Steinle, A., Pruschy, M., Polić, B., … Roth, P. (2018). NKG2D-dependent antitumor effects of chemotherapy and radiotherapy against glioblastoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 24(4), 882–895. https://doi.org/10.1158/1078-0432.CCR-17-1766 Weiss, T., Schneider, H., Silginer, M., Steinle, A., Pruschy, M., Polić, B., … Roth, P. (2018). NKG2D-dependent antitumor effects of chemotherapy and radiotherapy against glioblastoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 24(4), 882–895. https://​doi.​org/​10.​1158/​1078-0432.​CCR-17-1766
139.
go back to reference Parker, S., McDowall, C., Sanchez-Perez, L., Osorio, C., Duncker, P. C., Briley, A., … Chandramohan, V. (2023). Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models. Science Translational Medicine, 15(682), eabn5649. https://doi.org/10.1126/scitranslmed.abn5649 Parker, S., McDowall, C., Sanchez-Perez, L., Osorio, C., Duncker, P. C., Briley, A., … Chandramohan, V. (2023). Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models. Science Translational Medicine, 15(682), eabn5649. https://​doi.​org/​10.​1126/​scitranslmed.​abn5649
141.
142.
143.
144.
go back to reference Kesarwani, P., Prabhu, A., Kant, S., Kumar, P., Graham, S. F., Buelow, K. L., … Chinnaiyan, P. (2018). Tryptophan metabolism contributes to radiation-induced immune checkpoint reactivation in glioblastoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 24(15), 3632–3643. https://doi.org/10.1158/1078-0432.CCR-18-0041 Kesarwani, P., Prabhu, A., Kant, S., Kumar, P., Graham, S. F., Buelow, K. L., … Chinnaiyan, P. (2018). Tryptophan metabolism contributes to radiation-induced immune checkpoint reactivation in glioblastoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 24(15), 3632–3643. https://​doi.​org/​10.​1158/​1078-0432.​CCR-18-0041
146.
go back to reference Fenstermaker, R. A., Ciesielski, M. J., Qiu, J., Yang, N., Frank, C. L., Lee, K. P., … Hutson, A. D. (2016). Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma. Cancer Immunology, Immunotherapy, 65(11), 1339–1352. https://doi.org/10.1007/s00262-016-1890-x Fenstermaker, R. A., Ciesielski, M. J., Qiu, J., Yang, N., Frank, C. L., Lee, K. P., … Hutson, A. D. (2016). Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma. Cancer Immunology, Immunotherapy, 65(11), 1339–1352. https://​doi.​org/​10.​1007/​s00262-016-1890-x
147.
148.
go back to reference Choi, B. D., Kuan, C.-T., Cai, M., Archer, G. E., Mitchell, D. A., Gedeon, P. C., … Sampson, J. H. (2013). Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma. Proceedings of the National Academy of Sciences, 110(1), 270–275. https://doi.org/10.1073/pnas.1219817110 Choi, B. D., Kuan, C.-T., Cai, M., Archer, G. E., Mitchell, D. A., Gedeon, P. C., … Sampson, J. H. (2013). Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma. Proceedings of the National Academy of Sciences, 110(1), 270–275. https://​doi.​org/​10.​1073/​pnas.​1219817110
149.
150.
go back to reference O’Rourke, D. M., Nasrallah, M. P., Desai, A., Melenhorst, J. J., Mansfield, K., Morrissette, J. J. D., … Maus, M. V. (2017). A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Science Translational Medicine, 9(399), eaaa0984. https://doi.org/10.1126/scitranslmed.aaa0984 O’Rourke, D. M., Nasrallah, M. P., Desai, A., Melenhorst, J. J., Mansfield, K., Morrissette, J. J. D., … Maus, M. V. (2017). A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Science Translational Medicine, 9(399), eaaa0984. https://​doi.​org/​10.​1126/​scitranslmed.​aaa0984
151.
152.
go back to reference Majzner, R. G., Theruvath, J. L., Nellan, A., Heitzeneder, S., Cui, Y., Mount, C. W., … Mackall, C. L. (2019). CAR T cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors. Clinical Cancer Research, 25(8), 2560–2574. https://doi.org/10.1158/1078-0432.CCR-18-0432 Majzner, R. G., Theruvath, J. L., Nellan, A., Heitzeneder, S., Cui, Y., Mount, C. W., … Mackall, C. L. (2019). CAR T cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors. Clinical Cancer Research, 25(8), 2560–2574. https://​doi.​org/​10.​1158/​1078-0432.​CCR-18-0432
153.
go back to reference Patterson, J. D., Henson, J. C., Breese, R. O., Bielamowicz, K. J., & Rodriguez, A. (2020). CAR T cell therapy for pediatric brain tumors. Frontiers in Oncology, 10. Retrieved from https://www.frontiersin.org/journals/oncology/articles/https://doi.org/10.3389/fonc.2020.01582 Patterson, J. D., Henson, J. C., Breese, R. O., Bielamowicz, K. J., & Rodriguez, A. (2020). CAR T cell therapy for pediatric brain tumors. Frontiers in Oncology, 10. Retrieved from https://​www.​frontiersin.​org/​journals/​oncology/​articles/​https://​doi.​org/​10.​3389/​fonc.​2020.​01582
154.
155.
go back to reference Shibuya, K., Okada, M., Suzuki, S., Seino, M., Seino, S., Takeda, H., & Kitanaka, C. (2014). Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells. Oncotarget, 6(2), 651–661.CrossRefPubMedCentral Shibuya, K., Okada, M., Suzuki, S., Seino, M., Seino, S., Takeda, H., & Kitanaka, C. (2014). Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells. Oncotarget, 6(2), 651–661.CrossRefPubMedCentral
158.
go back to reference Longhitano, L., Vicario, N., Tibullo, D., Giallongo, C., Broggi, G., Caltabiano, R., … Li Volti, G. (2022). Lactate induces the expressions of MCT1 and HCAR1 to promote tumor growth and progression in glioblastoma. Frontiers in Oncology, 12, 871798. https://doi.org/10.3389/fonc.2022.871798 Longhitano, L., Vicario, N., Tibullo, D., Giallongo, C., Broggi, G., Caltabiano, R., … Li Volti, G. (2022). Lactate induces the expressions of MCT1 and HCAR1 to promote tumor growth and progression in glioblastoma. Frontiers in Oncology, 12, 871798. https://​doi.​org/​10.​3389/​fonc.​2022.​871798
Metadata
Title
Glioblastoma stem cell metabolism and immunity
Publication date
26-03-2024
Published in
Cancer and Metastasis Reviews
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-024-10183-w
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine