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Review Article

GBM Immunotherapy: Macrophage Impacts

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References

  • Akkari, L., Bowman, R. L., Tessier, J., Klemm, F., Handgraaf, S. M., de Groot, M., Quail, D. F., Tillard, L., Gadiot, J., Huse, J. T., Brandsma, D., Westerga, J., Watts, C., & Joyce, J. A. (2020). Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance. Science Translational Medicine, 12(552), 7843–7843. https://doi.org/10.1126/scitranslmed.aaw7843
  • Anghileri, E., Patane, M., Di, I. N., Sambruni, I., Maffezzini, M., Milani, M., Maddaloni, L., Pollo, B., Eoli, M., & Pellegatta, S. (2021). Deciphering the labyrinthine system of the immune microenvironment in recurrent glioblastoma: recent original advances and lessons from clinical immunotherapeutic approaches. Cancers (Basel), 13(24), 13. https://doi.org/10.3390/cancers13246156
  • Bai, Y., Lathia, J. D., Zhang, P., Flavahan, W., Rich, J. N., & Mattson, M. P. (2014). Molecular targeting of TRF2 suppresses the growth and tumorigenesis of glioblastoma stem cells. Glia, 62(10), 1687–1698. https://doi.org/10.1002/glia.22708
  • Baker, K. (2018). Organoids provide an important window on inflammation in cancer. Cancers, 10(5), 151. https://doi.org/10.3390/cancers10050151
  • Benner, B., Good, L., Quiroga, D., Schultz, T. E., Kassem, M., Carson, W. E., Cherian, M. A., Sardesai, S., & Wesolowski, R. (2020). Pexidartinib, a novel small molecule CSF-1R inhibitor in use for tenosynovial giant cell tumor: A systematic review of pre-clinical and clinical development. Drug Design, Development and Therapy, 14, 1693–1704. https://doi.org/10.2147/DDDT.S253232
  • Buonfiglioli, A., & Hambardzumyan, D. (2021). Macrophages and microglia: The cerberus of glioblastoma. Acta neuropathologica communications, 9(1), 54. https://doi.org/10.1186/s40478-021-01156-z
  • Butowski, N., Colman, H., De Groot, J. F., Omuro, A. M., Nayak, L., Wen, P. Y., Cloughesy, T. F., Marimuthu, A., Haidar, S., Perry, A., Huse, J., Phillips, J., West, B. L., Nolop, K. B., Hsu, H. H., Ligon, K. L., Molinaro, A. M., & Prados, M. (2016). Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: An ivy foundation early phase clinical trials consortium phase II study. Neuro-Oncology, 18(4), 557–564. https://doi.org/10.1093/neuonc/nov245
  • Cannarile, M. A., Weisser, M., Jacob, W., Jegg, A. M., Ries, C. H., & Ruttinger, D. (2017). Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. The Journal for ImmunoTherapy of Cancer, 5(1), 53. https://doi.org/10.1186/s40425-017-0257-y
  • Cersosimo, F., Lonardi, S., Ulivieri, C., Martini, P., Morrione, A., Vermi, W., Giordano, A., & Giurisato, E. (2024). CSF-1R in cancer: More than a myeloid cell receptor. Cancers, 16(2), 282. https://doi.org/10.3390/cancers16020282
  • Chen, P., DePinho, R., Alan, W., Liang, X., Li, J., Chang, A., Henry, V. K., Lan, Z., Spring, D. J., Rao, G., Wang, Y. A., & DePinho, R. A. (2019). Symbiotic macrophage-glioma cell interactions reveal synthetic lethality in PTEN-null Glioma. Neuro-Oncology, 35(6), 868–884. https://doi.org/10.1016/j.ccell.2019.05.003
  • Chen, Z., Feng, X., Herting, C. J., Garcia, V. A., Nie, K., Pong, W. W., Rasmussen, R., Dwivedi, B., Seby, S., Wolf, S. A., Gutmann, D. H., & Hambardzumyan, D. (2017). Cellular and molecular identity of tumor-associated macrophages in glioblastoma. Cancer Research, 77(9), 2266–2278. https://doi.org/10.1158/0008-5472.CAN-16-2310
  • Chen, J., Fu, X., Wan, Y., Wang, Z., Jiang, D., & Shi, L. (2014). miR-125b inhibitor enhance the chemosensitivity of glioblastoma stem cells to temozolomide by targeting Bak1. Tumor Biology, 35(7), 6293–6302. https://doi.org/10.1007/s13277-014-1821-4
  • Chen, X., Gao, A., Zhang, F., Yang, Z., Wang, S., Fang, Y., Li, J., Wang, J., Shi, W., Wang, L., Zheng, Y., & Sun, Y. (2021). ILT4 inhibition prevents TAM- and dysfunctional T cell-mediated immunosuppression and enhances the efficacy of anti-PD-L1 therapy in NSCLC with EGFR activation. Theranostics, 11(7), 3392–3416. https://doi.org/10.7150/thno.52435
  • Chen, A. X., Gartrell, R. D., Zhao, J., Upadhyayula, P. S., Zhao, W., Yuan, J., Minns, H. E., Dovas, A., Bruce, J. N., Lasorella, A., Iavarone, A., Canoll, P., Sims, P. A., & Rabadan, R. (2021). Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker. Genome Medicine, 13(1), 88. https://doi.org/10.1186/s13073-021-00906-x
  • Cheng, P., Ma, Y., Gao, Z., & Duan, L. (2018). High mobility group box 1 (HMGB1) predicts invasion and poor prognosis of glioblastoma multiforme via activating AKT signaling in an autocrine pathway. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 24, 8916–8924. https://doi.org/10.12659/MSM.912104
  • Chen, P., Hsu, W. H., Han, J., Xia, Y., & DePinho, R. A. (2021). Cancer stemness meets immunity: From mechanism to therapy. Cell Reports, 34(1), 108597. https://doi.org/10.1016/j.celrep.2020.108597
  • Chitu, V., Gokhan, Ş., Nandi, S., Mehler, M. F., & Stanley, E. R. (2016). Emerging roles for CSF-1 receptor and its ligands in the nervous system. Trends in neurosciences, 39(6), 378–393. https://doi.org/10.1016/j.tins.2016.03.005
  • Choi, J., Mai, N., Jackson, C., Belcaid, Z., & Lim, M. (2018). It takes two: Potential therapies and insights involving microglia and macrophages in glioblastoma. Neuroimmunology and Neuroinflammation, 5(10), 42–42. https://doi.org/10.20517/2347-8659.2018.47
  • Cisneros Castillo, L. R., Oancea, A. D., Stullein, C., & Regnier-Vigouroux, A. (2016). A novel computer-assisted approach to evaluate multicellular tumor spheroid invasion assay. Scientific Reports, 6(1), 35099. https://doi.org/10.1038/srep35099
  • Codrici, E., Popescu, I. D., Tanase, C., & Enciu, A. M. (2022). Friends with benefits: Chemokines, glioblastoma-associated microglia/macrophages, and tumor microenvironment. International Journal of Molecular Sciences, 23(5), 2509. https://doi.org/10.3390/ijms23052509
  • Cohen, J. V., & Kluger, H. M. (2016). Systemic immunotherapy for the treatment of brain metastases. Frontiers in Oncology, 6, 49. https://doi.org/10.3389/fonc.2016.00049
  • Coniglio, S. J., Eugenin, E., Dobrenis, K., Stanley, E. R., West, B. L., Symons, M. H., & Segall, J. E. (2012). Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Molecular Medicine (Cambridge, Mass), 18(3), 519–527. https://doi.org/10.2119/molmed.2011.00217
  • Costa, P. M., Cardoso, A. L., Custodia, C., Cunha, P., de Almeida, L. P., & Pedroso de Lima, M. C. (2015). MiRNA-21 silencing mediated by tumor-targeted nanoparticles combined with sunitinib: A new multimodal gene therapy approach for glioblastoma. Journal of Controlled Release, 207, 31–39. https://doi.org/10.1016/j.jconrel.2015.04.002
  • Cui, X., Morales, R. T., Qian, W., Wang, H., Gagner, J. P., Dolgalev, I., Placantonakis, D., Zagzag, D., Cimmino, L., Snuderl, M., Lam, R. H. W., & Chen, W. (2018). Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis. Biomaterials, 161, 164–178. https://doi.org/10.1016/j.biomaterials.2018.01.053
  • Dai, X., Ye, L., Li, H., Dong, X., Tian, H., Gao, P., Dong, J., & Cheng, H. (2023). Crosstalk between microglia and neural stem cells influences the relapse of glioblastoma in GBM immunological microenvironment. Clinical Immunology (Orlando, Fla), 251, 109333. https://doi.org/10.1016/j.clim.2023.109333
  • Dammeijer, F., Lievense, L. A., Kaijen-Lambers, M. E., van Nimwegen, M., Bezemer, K., Hegmans, J. P., van Hall, T., Hendriks, R. W., & Aerts, J. G. (2017). Depletion of tumor-associated macrophages with a CSF-1R kinase inhibitor enhances antitumor immunity and survival induced by DC immunotherapy. Cancer Immunology Research, 5(7), 535–546. https://doi.org/10.1158/2326-6066.CIR-16-0309
  • Dapash, M., Hou, D., Castro, B., Lee-Chang, C., & Lesniak, M. S. (2021). The interplay between glioblastoma and its microenvironment. Cells, 10(9), 2257. https://doi.org/10.3390/cells10092257
  • Darmanis, S., Sloan, S. A., Croote, D., Mignardi, M., Chernikova, S., Samghababi, P., Zhang, Y., Neff, N., Kowarsky, M., Caneda, C., Li, G., Chang, S. D., Connolly, I. D., Li, Y., Barres, B. A., Gephart, M. H., & Quake, S. R. (2017). Single-cell RNA-Seq analysis of infiltrating neoplastic cells at the migrating front of human glioblastoma. Cell Reports, 21(5), 1399–1410. https://doi.org/10.1016/j.celrep.2017.10.030
  • Delcassian, D., Malecka, A. A., Opoku, D., Cabeza, V. P., Merry, C., & Jackson, A. M. (2019). Primary human macrophages are polarized towards pro-inflammatory 1 phenotypes in alginate hydrogels. bioRxiv, 824391. https://doi.org/10.1101/824391
  • DeNardo, D. G., & Ruffell, B. (2019). Macrophages as regulators of tumour immunity and immunotherapy. Nature Reviews Immunology, 19(6), 369–382. https://doi.org/10.1038/s41577-019-0127-6
  • DiModugno, F., Colosi, C., Trono, P., Antonacci, G., Ruocco, G., & Nistico, P. (2019). 3D models in the new era of immune oncology: Focus on T cells, CAF and ECM. Journal of Experimental and Clinical Cancer Research, 38(1), 117. https://doi.org/10.1186/s13046-019-1086-2
  • Ding, A. S., Routkevitch, D., Jackson, C., & Lim, M. (2019). Targeting myeloid cells in combination treatments for glioma and other tumors. Frontiers in Immunology, 10, 1715–1715. https://doi.org/10.3389/fimmu.2019.01715
  • Dusoswa, S. A., Verhoeff, J., Abels, E., Méndez-Huergo, S. P., Croci, D. O., Kuijper, L. H., de Miguel, E., Wouters, V. M. C. J., Best, M. G., Rodriguez, E., Cornelissen, L. A. M., van Vliet, S. J., Wesseling, P., Breakefield, X. O., Noske, D. P., Würdinger, T., Broekman, M. L. D., Rabinovich, G. A., van Kooyk, Y., & Garcia-Vallejo, J. J. (2020). Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin. Proceedings of the National Academy of Sciences of the United States of America, 117(7), 3693–3703. https://doi.org/10.1073/pnas.1907921117
  • Fedele, M., Cerchia, L., Pegoraro, S., Sgarra, R., & Manfioletti, G. (2019). Proneural-mesenchymal transition: Phenotypic plasticity to acquire multitherapy resistance in glioblastoma. International Journal of Molecular Sciences, 20(11), 2746. https://doi.org/10.3390/ijms20112746
  • Flores-Toro, J. A., Luo, D., Gopinath, A., Sarkisian, M. R., Campbell, J. J., Charo, I. F., Singh, R., Schall, T. J., Datta, M., Jain, R. K., Mitchell, D. A., & Harrison, J. K. (2020). CCR2 inhibition reduces tumor myeloid cells and unmasks a checkpoint inhibitor effect to slow progression of resistant murine gliomas. Proceedings of the National Academy of Sciences of the United States of America, 117(2), 1129–1138. https://doi.org/10.1073/pnas.1910856117
  • Galluzzi, L., Vacchelli, E., Bravo-San Pedro, J. M., Buque, A., Senovilla, L., Baracco, E. E., Bloy, N., Castoldi, F., Abastado, J.-P., Agostinis, P., Apte, R. N., Aranda, F., Ayyoub, M., Beckhove, P., Blay, J.-Y., Bracci, L., Caignard, A., Castelli, C., … Zou, W. (2014). Classification of current anticancer immunotherapies. Oncotarget, 5(24), 12472–12508. https://doi.org/10.18632/oncotarget.2998
  • Gao, H., Yang, Z., Cao, S., Xiong, Y., Zhang, S., Pang, Z., & Jiang, X. (2014). Tumor cells and neovasculature dual targeting delivery for glioblastoma treatment. Biomaterials, 35(7), 2374–2382. https://doi.org/10.1016/j.biomaterials.2013.11.076
  • Garris, C. S., Blaho, V. A., Hla, T., & Han, M. H. (2014). Sphingosine-1-phosphate receptor 1 signalling in T cells: Trafficking and beyond. Immunology, 142(3), 347–353. https://doi.org/10.1111/imm.12272
  • Geraldo, L. H., Xu, Y., Jacob, L., Pibouin-Fragner, L., Rao, R., Maissa, N., Verreault, M., Lemaire, N., Knosp, C., Lesaffre, C., Daubon, T., Dejaegher, J., Solie, L., Rudewicz, J., Viel, T., Tavitian, B., De Vleeschouwer, S., Sanson, M., … Eichmann, A. (2021). SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia. Journal of Clinical Investigation, 131(16), e141083. https://doi.org/10.1172/JCI141083
  • Gholamin, S., Mitra, S. S., Feroze, A. H., Liu, J., Kahn, S. A., Zhang, M., Esparza, R., Richard, C., Ramaswamy, V., Remke, M., Volkmer, A. K., Willingham, S., Ponnuswami, A., McCarty, A., Lovelace, P., Storm, T. A., Schubert, S., Hutter, G., … Weissman, I. L. (2017). Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Science Translational Medicine, 9(381), eaaf2968. https://doi.org/10.1126/scitranslmed.aaf2968
  • Ginhoux, F., Lim, S., Hoeffel, G., Low, D., & Huber, T. (2013). Origin and differentiation of microglia. Frontiers in Cellular Neuroscience, 7, 45. https://doi.org/10.3389/fncel.2013.00045
  • Goenka, A., Tiek, D., Song, X., Huang, T., Hu, B., & Cheng, S. Y. (2021). The many facets of therapy resistance and tumor recurrence in glioblastoma. Cells, 10(3), 1–21. https://doi.org/10.3390/cells10030484
  • Gonzalez-Gomez, P., Anselmo, N. P., & Mira, H. (2014). BMPs as therapeutic targets and biomarkers in astrocytic glioma. BioMed Research International, 2014, 549742. https://doi.org/10.1155/2014/549742
  • Goswami, S., Walle, T., Cornish, A. E., Basu, S., Anandhan, S., Fernandez, I., Vence, L., Blando, J., Zhao, H., Yadav, S. S., Ott, M., Kong, L. Y., Heimberger, A. B., de Groot, J., Sepesi, B., Overman, M., Kopetz, S., Allison, J. P., Pe’er, D., & Sharma, P. (2020). Immune profiling of human tumors identifies CD73 as a combinatorial target in glioblastoma. Nature Medicine, 26(1), 39–46. https://doi.org/10.1038/s41591-019-0694-x
  • Hartley, G., Regan, D., Guth, A., & Dow, S. (2017). Regulation of PD-L1 expression on murine tumor-associated monocytes and macrophages by locally produced TNF-α. Cancer Immunology, Immunotherapy: CII, 66(4), 523–535. https://doi.org/10.1007/s00262-017-1955-5
  • Held-Feindt, J., Hattermann, K., Muerkoster, S. S., Wedderkopp, H., Knerlich-Lukoschus, F., Ungefroren, H., Mehdorn, H. M., & Mentlein, R. (2010). CX3CR1 promotes recruitment of human glioma-infiltrating microglia/macrophages (GIMs). Experimental Cell Research, 316(9), 1553–1566. https://doi.org/10.1016/j.yexcr.2010.02.018
  • Herter, S., Morra, L., Schlenker, R., Sulcova, J., Fahrni, L., Waldhauer, I., Lehmann, S., Reisländer, T., Agarkova, I., Kelm, J. M., Klein, C., Umana, P., & Bacac, M. (2017). A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents. Cancer Immunology Immunotherapy, 66(1), 129–140. https://doi.org/10.1007/s00262-016-1927-1
  • Himes, B. T., Geiger, P. A., Ayasoufi, K., Bhargav, A. G., Brown, D. A., & Parney, I. F. (2021). Immunosuppression in glioblastoma: Current understanding and therapeutic implications. Frontiers in Oncology, 11, 770561. https://doi.org/10.3389/fonc.2021.770561
  • Hutter, G., Theruvath, J., Graef, C. M., Zhang, M., Schoen, M. K., Manz, E. M., Bennett, M. L., Olson, A., Azad, T. D., Sinha, R., Chan, C., Assad Kahn, S., Gholamin, S., Wilson, C., Grant, G., He, J., Weissman, I. L., Mitra, S. S., & Cheshier, S. H. (2019). Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma. Proceedings of the National Academy of Sciences of the United States of America, 116(3), 997–1006. https://doi.org/10.1073/pnas.1721434116
  • Jackson, C. M., Kochel, C. M., Nirschl, C. J., Durham, N. M., Ruzevick, J., Alme, A., Francica, B. J., Elias, J., Daniels, A., Dubensky, T. W., Lauer, P., Brockstedt, D. G., Baxi, E. G., Calabresi, P. A., Taube, J. M., Pardo, C. A., Brem, H., Pardoll, D. M., Lim, M., & Drake, C. G. (2016). Systemic tolerance mediated by melanoma brain tumors is reversible by radiotherapy and vaccination. Clinical Cancer Research, 22(5), 1161–1172. https://doi.org/10.1158/1078-0432.CCR-15-1516
  • Jarosz-Biej, M., Smolarczyk, R., Cichon, T., & Kułach, N. (2019). Tumor microenvironment as a “game changer” in cancer radiotherapy. International Journal of Molecular Sciences, 20(13), 3212. https://doi.org/10.3390/ijms20133212
  • Jung, J., Kim, L. J., Wang, X., Wu, Q., Sanvoranart, T., Hubert, C. G., Prager, B. C., Wallace, L. C., Jin, X., Mack, S. C., & Rich, J. N. (2017). Nicotinamide metabolism regulates glioblastoma stem cell maintenance. JCI Insight, 2(10), e90019. https://doi.org/10.1172/jci.insight.90019
  • Khan, F., Pang, L., Dunterman, M., Lesniak, M. S., Heimberger, A. B., & Chen, P. (2023). Macrophages and microglia in glioblastoma: Heterogeneity, plasticity, and therapy. The Journal of Clinical Investigation, 133(1), e163446. https://doi.org/10.1172/JCI163446
  • Kim, H., Cha, J., Jang, M., & Kim, P. (2019). Hyaluronic acid-based extracellular matrix triggers spontaneous M2-like polarity of monocyte/macrophage. Biomaterials Science, 7(6), 2264–2271. https://doi.org/10.1039/C9BM00155G
  • Kreatsoulas, D., Bolyard, C., Wu, B. X., Cam, H., Giglio, P., & Li, Z. (2022). Translational landscape of glioblastoma immunotherapy for physicians: Guiding clinical practice with basic scientific evidence. Journal of Hematology and Oncology, 15(1), 80. https://doi.org/10.1186/s13045-022-01298-0
  • Kumthekar, P., Ko, C. H., Paunesku, T., Dixit, K., Sonabend, A. M., Bloch, O., Tate, M., Schwartz, M., Zuckerman, L., Lezon, R., Lukas, R. V., Jovanovic, B., McCortney, K., Colman, H., Chen, S., Lai, B., Antipova, O., Deng, J., … Horbinski, C. (2021). A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma. Science Translational Medicine, 13(584), eabb3945. https://doi.org/10.1126/scitranslmed.abb3945
  • Kuppner, M. C., Hamou, M. F., Sawamura, Y., Bodmer, S., & de Tribolet, N. (1989). Inhibition of lymphocyte function by glioblastoma-derived transforming growth factor β2. Journal of Neurosurgery, 71(2), 211–217. https://doi.org/10.3171/jns.1989.71.2.0211
  • Larsen, A. M. H., Kuczek, D. E., Kalvisa, A., Siersbæk, M. S., Thorseth, M. L., Johansen, A. Z., Carretta, M., Grøntved, L., Vang, O., & Madsen, D. H. (2020). Collagen density modulates the immunosuppressive functions of macrophages. Journal of Immunology, 205(5), 1461–1472. https://doi.org/10.4049/jimmunol.1900789
  • Lee, C., Kim, G. R., Yoon, J., Kim, S. E., Yoo, J. S., & Piao, Y. (2018). In vivo delineation of glioblastoma by targeting tumor-associated macrophages with near-infrared fluorescent silica coated iron oxide nanoparticles in orthotopic xenografts for surgical guidance. Scientific Reports, 8(1), 11122. https://doi.org/10.1038/s41598-018-29424-4
  • Li, J., Kaneda, M. M., Ma, J., Chen, C. C., Shepard, R. M., Patel, K., Koga, T., Sarver, A., Furnari, F., Xu, B., Dhawan, S., Ning, J., Zhu, H., Wu, A., You, G., Jiang, T., Venteicher, A. S., Rich, J. N., … Varner, J. A. (2021). PI3Kγ inhibition suppresses microglia/TAM accumulation in glioblastoma microenvironment to promote exceptional temozolomide response. Proceedings of the National Academy of Sciences of the United States of America, 118(16), e2009290118. https://doi.org/10.1073/pnas.2009290118
  • Lin, J. G., Kang, C. C., Zhou, Y., Huang, H., Herr, A. E., & Kumar, S. (2018). Linking invasive motility to protein expression in single tumor cells. Lab on a Chip, 18(2), 371–384. https://doi.org/10.1039/C7LC01008G
  • Linville, R. M., Boland, N. F., Covarrubias, G., Price, G. M., & Tien, J. (2016). Physical and chemical signals that promote vascularization of capillary-scale channels. Cellular and Molecular Bioengineering, 9(1), 73–84. https://doi.org/10.1007/s12195-016-0429-8
  • Li, W., Wu, F., Zhao, S., Shi, P., Wang, S., & Cui, D. (2022). Correlation between PD-1/PD-L1 expression and polarization in tumor-associated macrophages: A key player in tumor immunotherapy. Cytokine & Growth Factor Reviews, 67, 49–57. https://doi.org/10.1016/j.cytogfr.2022.07.004
  • Lowther, D. E., Goods, B. A., Lucca, L. E., Lerner, B. A., Raddassi, K., van Dijk, D., Hernandez, A. L., Duan, X., Gunel, M., Coric, V., Krishnaswamy, S., Love, J. C., & Hafler, D. A. (2016). PD-1 marks dysfunctional regulatory T cells in malignant gliomas. JCI Insight, 1(5), e85935. https://doi.org/10.1172/jci.insight.85935
  • Lugano, R., Ramachandran, M., & Dimberg, A. (2020). Tumor angiogenesis: Causes, consequences, challenges and opportunities. Cellular and Molecular Life Sciences, 77(9), 1745–1770. https://doi.org/10.1007/s00018-019-03351-7
  • Magill, S. T., Han, S. J., Li, J., & Berger, M. S. (2018). Resection of primary motor cortex tumors: Feasibility and surgical outcomes. Journal of Neurosurgery, 129(4), 961–972. https://doi.org/10.3171/2017.5.JNS163045
  • Ma, D., Liu, S., Lal, B., Wei, S., Wang, S., Zhan, D., Zhang, H., Lee, R. S., Gao, P., Lopez-Bertoni, H., Ying, M., Li, J. J., Laterra, J., Wilson, M. A., & Xia, S. (2019). Extracellular matrix protein tenascin C increases phagocytosis mediated by CD47 loss of function in Glioblastoma. Cancer Research, 79(10), 2697–2708. https://doi.org/10.1158/0008-5472.CAN-18-3125
  • Mantovani, A., Marchesi, F., Malesci, A., Laghi, L., & Allavena, P. (2017). Tumour-associated macrophages as treatment targets in oncology. Nature Reviews, Clinical Oncology, 14(7), 399–416. https://doi.org/10.1038/nrclinonc.2016.217
  • Medikonda, R., Dunn, G., Rahman, M., Fecci, P., & Lim, M. (2021). A review of glioblastoma immunotherapy. Journal of Neuro-Oncology, 151(1), 41–53. https://doi.org/10.1007/s11060-020-03448-1
  • Mercurio, L., Ajmone-Cat, M. A., Cecchetti, S., Ricci, A., Bozzuto, G., Molinari, A., Manni, I., Pollo, B., Scala, S., Carpinelli, G., & Minghetti, L. (2016). Targeting CXCR4 by a selective peptide antagonist modulates tumor microenvironment and microglia reactivity in a human glioblastoma model. Journal of Experimental & Clinical Cancer Research, 35(1), 55. https://doi.org/10.1186/s13046-016-0326-y
  • Mestas, J., & Hughes, C. C. W. (2004). Immunology of mice and not men: Differences between mouse and human immunology. The Journal of Immunology, 172(5), 2731–2738. https://doi.org/10.4049/jimmunol.172.5.2731
  • Mo, F., Pellerino, A., Soffietti, R., & Ruda, R. (2021). Blood-brain barrier in brain tumors: Biology and clinical relevance. International Journal of Molecular Sciences, 22(23), 12654. https://doi.org/10.3390/ijms222312654
  • Mora, R., Abschuetz, A., Kees, T., Dokic, I., Joschko, N., Kleber, S., Geibig, R., Mosconi, E., Zentgraf, H., Martin‐Villalba, A., & Régnier‐Vigouroux, A. (2009). TNF-α- and TRAIL-resistant glioma cells undergo autophagy-dependent cell death induced by activated microglia. Glia, 57(5), 561–581. https://doi.org/10.1002/glia.20785
  • Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J., Ivashkiv, L., Lawrence, T., Locati, M., Mantovani, A., Martinez, F., Mege, J.-L., Mosser, D., Natoli, G., Saeij, J., Schultze, J., … Vogel, S. (2014). Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity, 41(1), 14–20. https://doi.org/10.1016/j.immuni.2014.06.008
  • Nabors, L. B., Portnow, J., Ahluwalia, M., Baehring, J., Brem, H., Brem, S., Butowski, N., Campian, J. L., Clark, S. W., Fabiano, A. J., Forsyth, P., Hattangadi-Gluth, J., Holdhoff, M., Horbinski, C., Junck, L., Kaley, T., Kumthekar, P., Loeffler, J. S., … Bergman, M. A. (2020). Central nervous system cancers, version 3.2020. Journal of the National Comprehensive Cancer Network, 18(11), 1537–1570. https://doi.org/10.6004/jnccn.2020.0052
  • Nakod, P. S., Kim, Y., & Rao, S. S. (2020). Three-dimensional biomimetic hyaluronic acid hydrogels to investigate glioblastoma stem cell behaviors. Biotechnology and Bioengineering, 117(2), 511–522. https://doi.org/10.1002/bit.27219
  • Nanta, R., Shrivastava, A., Sharma, J., Shankar, S., & Srivastava, R. K. (2019). Inhibition of sonic hedgehog and PI3K/Akt/mTOR pathways cooperate in suppressing survival, self-renewal and tumorigenic potential of glioblastoma-initiating cells. Molecular and Cellular Biochemistry, 454(1–2), 11–23. https://doi.org/10.1007/s11010-018-3448-z
  • Noy, R., & Pollard, J. W. (2014). Tumor-associated macrophages: From mechanisms to therapy. Immunity, 41(1), 49–61. https://doi.org/10.1016/j.immuni.2014.06.010
  • Pachocki, C. J., & Hol, E. M. (2022). Current perspectives on diffuse midline glioma and a different role for the immune microenvironment compared to glioblastoma. Journal of Neuroinflammation, 19(1), 276. https://doi.org/10.1186/s12974-022-02630-8
  • Padfield, E., Ellis, H. P., & Kurian, K. M. (2015). Current therapeutic advances targeting EGFR and EGFRvIII in glioblastoma. Frontiers in Oncology, 5, 5. https://doi.org/10.3389/fonc.2015.00005
  • Pittet, M. J., Michielin, O., & Migliorini, D. (2022). Clinical relevance of tumour-associated macrophages. Nature Reviews, Clinical Oncology, 19(6), 402–421. https://doi.org/10.1038/s41571-022-00620-6
  • Platten, M., Kretz, A., Naumann, U., Aulwurm, S., Egashira, K., Isenmann, S., & Weller, M. (2003). Monocyte chemoattractant protein–1 increases microglial infiltration and aggressiveness of gliomas. Annals of Neurology, 54(3), 388–392. https://doi.org/10.1002/ana.10679
  • Pombo Antunes, A. R., Scheyltjens, I., Lodi, F., Messiaen, J., Antoranz, A., Duerinck, J., Kancheva, D., Martens, L., De Vlaminck, K., Van Hove, H., Kjølner Hansen, S. S., Bosisio, F. M., Van der Borght, K., De Vleeschouwer, S., Sciot, R., Bouwens, L., Verfaillie, M., Vandamme, N., … Van Ginderachter, J. A. (2021). Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization. Nature Neuroscience, 24(4), 595–610. https://doi.org/10.1038/s41593-020-00789-y
  • Prabhu, A., Kesarwani, P., Kant, S., Graham, S. F., & Chinnaiyan, P. (2017). Histologically defined intratumoral sequencing uncovers evolutionary cues into conserved molecular events driving gliomagenesis. Neuro-Oncology, 19(12), 1599–1606. https://doi.org/10.1093/neuonc/nox100
  • Pyonteck, S. M., Akkari, L., Schuhmacher, A. J., Bowman, R. L., Sevenich, L., Quail, D. F., Olson, O. C., Quick, M. L., Huse, J. T., Teijeiro, V., Setty, M., Leslie, C. S., Oei, Y., Pedraza, A., Zhang, J., Brennan, C. W., Sutton, J. C., Holland, E. C., Daniel, D., & Joyce, J. A. (2013). CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nature Medicine, 19(10), 1264–1272. https://doi.org/10.1038/nm.3337
  • Qin, W., Hu, L., Zhang, X., Jiang, S., Li, J., Zhang, Z., & Wang, X. (2019). The diverse function of PD-1/PD-L pathway beyond cancer. Frontiers in Immunology, 10, 2298. https://doi.org/10.3389/fimmu.2019.02298
  • Quail, D. F., Bowman, R. L., Akkari, L., Quick, M. L., Schuhmacher, A. J., Huse, J. T., Holland, E. C., Sutton, J. C., & Joyce, J. A. (2016). The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science, 352(6288), aad3018. https://doi.org/10.1126/science.aad3018
  • Rianna, C., Radmacher, M., Kumar, S., & Discher, D. (2020). Direct evidence that tumor cells soften when navigating confined spaces. Molecular Biology of the Cell, 31(16), 1726–1734. https://doi.org/10.1091/mbc.E19-10-0588
  • Roth, P., Silginer, M., Goodman, S. L., Hasenbach, K., Thies, S., Maurer, G., Schraml, P., Tabatabai, G., Moch, H., Tritschler, I., & Weller, M. (2013). Integrin control of the transforming growth factor-β pathway in glioblastoma. Brain, 136(2), 564–576. https://doi.org/10.1093/brain/aws351
  • Scott, D. W., & Gascoyne, R. D. (2014). The tumour microenvironment in B cell lymphomas. Nature Reviews Cancer, 14(8), 517–534. https://doi.org/10.1038/nrc3774
  • Seliger, C., Meyer, A. L., Leidgens, V., Rauer, L., Moeckel, S., Jachnik, B., Proske, J., Dettmer, K., Rothhammer-Hampl, T., Kaulen, L. D., Riemenschneider, M. J., Oefner, P. J., Kreutz, M., Schmidt, N.-O., Merrill, M., Uhl, M., Renner, K., Vollmann-Zwerenz, A., Proescholdt, M., & Hau, P. (2022). Metabolic heterogeneity of brain tumor cells of proneural and mesenchymal origin. International Journal of Molecular Sciences, 23(19), 11629. https://doi.org/10.3390/ijms231911629
  • Shao, Z., Tan, Y., Shen, Q., Hou, L., Yao, B., Qin, J., Xu, P., Mao, C., Chen, L.-N., Zhang, H., Shen, D.-D., Zhang, C., Li, W., Du, X., Li, F., Chen, Z.-H., Jiang, Y., Xu, H. E., … Zhang, Y. (2022). Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3. Cell Discovery, 8(1), 44. https://doi.org/10.1038/s41421-022-00403-4
  • Sharpe, A. H., & Pauken, K. E. (2018). The diverse functions of the PD1 inhibitory pathway. Nature Reviews, Immunology, 18(3), 153–167. https://doi.org/10.1038/nri.2017.108
  • Shin, D. H., Xuan, S., Kim, W. Y., Bae, G. U., & Kim, J. S. (2014). CD133 antibody-conjugated immunoliposomes encapsulating gemcitabine for targeting glioblastoma stem cells. Journal of Materials Chemistry B, 2(24), 3771–3781. https://doi.org/10.1039/c4tb00185k
  • Stanley, E. R., & Chitu, V. (2014). CSF-1 receptor signaling in myeloid cells. Cold Spring Harbor Perspectives in Biology, 6(6), a021857–a021857. https://doi.org/10.1101/cshperspect.a021857
  • Takenaka, M. C., Gabriely, G., Rothhammer, V., Mascanfroni, I. D., Wheeler, M. A., Chao, C. C., Gutiérrez-Vázquez, C., Kenison, J., Tjon, E. C., Barroso, A., Vandeventer, T., de Lima, K. A., Rothweiler, S., Mayo, L., Ghannam, S., Zandee, S., Healy, L., Sherr, D., … Weiner, H. L. (2019). Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nature Neuroscience, 22(5), 729–740. https://doi.org/10.1038/s41593-019-0370-y
  • Tan, I. L., Arifa, R. D. N., Rallapalli, H., Kana, V., Lao, Z., Sanghrajka, R. M., Sumru Bayin, N., Tanne, A., Wojcinski, A., Korshunov, A., Bhardwaj, N., Merad, M., Turnbull, D. H., Lafaille, J. J., & Joyner, A. L. (2021). CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic hedgehog-medulloblastoma model. Oncogene, 40(2), 396–407. https://doi.org/10.1038/s41388-020-01536-0
  • Tap, W. D., Wainberg, Z. A., Anthony, S. P., Ibrahim, P. N., Zhang, C., Healey, J. H., Chmielowski, B., Staddon, A. P., Cohn, A. L., Shapiro, G. I., Keedy, V. L., Singh, A. S., Puzanov, I., Kwak, E. L., Wagner, A. J., Von Hoff, D. D., Weiss, G. J., Ramanathan, R. K., … Tong-Starksen, S. (2015). Structure-guided blockade of CSF1R kinase in tenosynovial giant-cell tumor. The New England Journal of Medicine, 373(5), 428–437. https://doi.org/10.1056/NEJMoa1411366
  • Thaci, B., Ulasov, I. V., Ahmed, A. U., Ferguson, S. D., Han, Y., & Lesniak, M. S. (2013). Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation. Gene Therapy, 20(3), 318–327. https://doi.org/10.1038/gt.2012.42
  • Tibbitt, M. W., & Anseth, K. S. (2009). Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnology and Bioengineering, 103(4), 655–663. https://doi.org/10.1002/bit.22361
  • Torrisi, F., D’Aprile, S., Denaro, S., Pavone, A. M., Alberghina, C., Zappala, A., Giuffrida, R., Salvatorelli, L., Broggi, G., Magro, G. G., Calabrese, V., Vicario, N., & Parenti, R. (2023). Epigenetics and metabolism reprogramming interplay into glioblastoma: Novel insights on immunosuppressive mechanisms. Antioxidants, 12(2), 220. https://doi.org/10.3390/antiox12020220
  • Truong, D., Fiorelli, R., Barrientos, E. S., Melendez, E. L., Sanai, N., Mehta, S., & Nikkhah, M. (2019). A three-dimensional (3D) organotypic microfluidic model for glioma stem cells – Vascular interactions. Biomaterials, 198, 63–77. https://doi.org/10.1016/j.biomaterials.2018.07.048
  • von Roemeling, C. A., Wang, Y., Qie, Y., Yuan, H., Zhao, H., Liu, X., Yang, Z., Yang, M., Deng, W., Bruno, K. A., Chan, C. K., Lee, A. S., Rosenfeld, S. S., Yun, K., Johnson, A. J., Mitchell, D. A., Jiang, W., & Kim, B. Y. S. (2020). Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity. Nature Communications, 11(1), 1508. https://doi.org/10.1038/s41467-020-15129-8
  • Walentynowicz, K. A., Ochocka, N., Pasierbinska, M., Wojnicki, K., Stepniak, K., Mieczkowski, J., Ciechomska, I. A., & Kaminska, B. (2018). In search for reliable markers of glioma-induced polarization of microglia. Frontiers in Immunology, 9, 1329. https://doi.org/10.3389/fimmu.2018.01329
  • Wang, X., Ding, H., Li, Z., Peng, Y., Tan, H., Wang, C., Huang, G., Li, W., Ma, G., & Wei, W. (2022). Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects. Signal Transduction and Targeted Therapy, 7(1), 74. https://doi.org/10.1038/s41392-022-00894-3
  • Wang, Q., Hu, B., Hu, X., Kim, H., Squatrito, M., Scarpace, L., deCarvalho, A. C., Lyu, S., Li, P., Li, Y., Barthel, F., Cho, H. J., Lin, Y.-H., Satani, N., Martinez-Ledesma, E., Zheng, S., Chang, E., Sauvé, C. E. G., … Nam, D.-H. (2017). Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell, 32(1), 42–56 e46. https://doi.org/10.1016/j.ccell.2017.06.003
  • Wang, Y., Wang, D., Yang, L., & Zhang, Y. (2022). Metabolic reprogramming in the immunosuppression of tumor-associated macrophages. Chinese Medical Journal, 135(20), 2405–2416. https://doi.org/10.1097/CM9.0000000000002426
  • Wang, S. C., Yu, C. F., Hong, J. H., Tsai, C. S., & Chiang, C. S. (2013). Radiation therapy-induced tumor invasiveness is associated with SDF-1-regulated macrophage mobilization and vasculogenesis. PLOSONE, 8(8), e69182. https://doi.org/10.1371/journal.pone.0069182
  • Wang, G., Zhong, K., Wang, Z., Zhang, Z., Tang, X., Tong, A., & Zhou, L. (2022). Tumor-associated microglia and macrophages in glioblastoma: From basic insights to therapeutic opportunities. Frontiers in Immunology, 13, 964898. https://doi.org/10.3389/fimmu.2022.964898
  • Wei, J., Marisetty, A., Schrand, B., Gabrusiewicz, K., Hashimoto, Y., Ott, M., Grami, Z., Kong, L.-Y., Ling, X., Caruso, H., Zhou, S., Wang, Y. A., Fuller, G. N., Huse, J., Gilboa, E., Kang, N., Huang, X., Verhaak, R., Li, S., & Heimberger, A. B. (2019). Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target. Journal of Clinical Investigation, 129(1), 137–149. https://doi.org/10.1172/JCI121266
  • Wischhusen, J., Friese, M. A., Mittelbronn, M., Meyermann, R., & Weller, M. (2005). HLA-E protects glioma cells from NKG2D-Mediated immune responses in vitro: implications for immune escape in vivo. Journal of Neuropathology & Experimental Neurology, 64(6), 523–528. https://doi.org/10.1093/jnen/64.6.523
  • Wolf, K. J., Chen, J., Coombes, J. D., Aghi, M. K., & Kumar, S. (2019). Dissecting and rebuilding the glioblastoma microenvironment with engineered materials. Nature Reviews Materials, 4(10), 651–668. https://doi.org/10.1038/s41578-019-0135-y
  • Xiao, W., Wang, S., Zhang, R., Sohrabi, A., Yu, Q., Liu, S., Ehsanipour, A., Liang, J., Bierman, R. D., Nathanson, D. A., & Seidlits, S. K. (2020). Bioengineered scaffolds for 3D culture demonstrate extracellular matrix-mediated mechanisms of chemotherapy resistance in glioblastoma. Matrix Biology, 85-86, 128–146. https://doi.org/10.1016/j.matbio.2019.04.003
  • Xiao, &., Wang, &., Zhao, &., Ji, &., Xiang, C., Li, T. (2022). A novel defined risk signature of interferon response genes predicts the prognosis and correlates with immune infiltration in glioblastoma. Mathematical Biosciences and Engineering: MBE, 19(9), 9481–9504. https://doi.org/10.3934/mbe.2022441
  • Xuan, W., Lesniak, M. S., James, C. D., Heimberger, A. B., & Chen, P. (2021). Context-dependent glioblastoma–macrophage/microglia symbiosis and associated mechanisms. Trends in Immunology, 42(4), 280–292. https://doi.org/10.1016/j.it.2021.02.004
  • Yagi, T., Baba, Y., Okadome, K., Kiyozumi, Y., Hiyoshi, Y., Ishimoto, T., Iwatsuki, M., Miyamoto, Y., Yoshida, N., Watanabe, M., Komohara, Y., & Baba, H. (2019). Tumour-associated macrophages are associated with poor prognosis and programmed death ligand 1 expression in oesophageal cancer. European Journal of Cancer (Oxford, England: 1990), 111, 38–49. https://doi.org/10.1016/j.ejca.2019.01.018
  • Yang, F., He, Z., Duan, H., Zhang, D., Li, J., Yang, H., Dorsey, J. F., Zou, W., Nabavizadeh, S. A., Bagley, S. J., Abdullah, K., Brem, S., Zhang, L., Xu, X., Byrne, K. T., Vonderheide, R. H., Gong, Y., & Fan, Y. (2021). Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40. Nature Communications, 12(1), 3424. https://doi.org/10.1038/s41467-021-23832-3
  • Yan, D., Kowal, J., Akkari, L., Schuhmacher, A. J., Huse, J. T., West, B. L., & Joyce, J. A. (2017). Inhibition of colony stimulating factor-1 receptor abrogates microenvironment-mediated therapeutic resistance in gliomas. Oncogene, 36(43), 6049–6058. https://doi.org/10.1038/onc.2017.261
  • Yin, J., Kim, S. S., Choi, E., Oh, Y. T., Lin, W., Kim, T. H., Sa, J. K., Hong, J. H., Park, S. H., Kwon, H. J., Jin, X., You, Y., Kim, J. H., Kim, H., Son, J., Lee, J., Nam, D.-H., Choi, K. S., … Kim, J. H. (2020). ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages. Nature Communications, 11(1), 2978. https://doi.org/10.1038/s41467-020-16789-2
  • Yin, J., Oh, Y. T., Kim, J. Y., Kim, S. S., Choi, E., Kim, T. H., Hong, J. H., Chang, N., Cho, H. J., Sa, J. K., Kim, J. C., Kwon, H. J., Park, S., Lin, W., Nakano, I., Gwak, H.-S., Yoo, H., Lee, S.-H., … Park, M.-J. (2017). Transglutaminase 2 inhibition reverses mesenchymal transdifferentiation of glioma stem cells by regulating C/EBPβ signaling. Cancer Research, 77(18), 4973–4984. https://doi.org/10.1158/0008-5472.CAN-17-0388
  • Yin, J., Valin, K. L., Dixon, M. L., & Leavenworth, J. W. (2017). The role of microglia and macrophages in CNS homeostasis, autoimmunity, and cancer. Journal of Immunology Research, 2017, 5150678. https://doi.org/10.1155/2017/5150678
  • Zhai, K., Huang, Z., Huang, Q., Tao, W., Fang, X., Zhang, A., Li, X., Stark, G. R., Hamilton, T. A., & Bao, S. (2021). Pharmacological inhibition of BACE1 suppresses glioblastoma growth by stimulating macrophage phagocytosis of tumor cells. Nature Cancer, 2(11), 1136–1151. https://doi.org/10.1038/s43018-021-00267-9
  • Zhang, B., Peticone, C., Murthy, S. K., & Radisic, M. (2013). A standalone perfusion platform for drug testing and target validation in micro-vessel networks. Biomicrofluidics, 7(4), 44125. https://doi.org/10.1063/1.4818837
  • Zhao, Y., Qu, Y., Hao, C., & Yao, W. (2023). PD-1/PD-L1 axis in organ fibrosis. Frontiers in Immunology, 14, 1145682. https://doi.org/10.3389/fimmu.2023.1145682
  • Zhou, W., Ke, S. Q., Huang, Z., Flavahan, W., Fang, X., Paul, J., Wu, L., Sloan, A. E., McLendon, R. E., Li, X., Rich, J. N., & Bao, S. (2015). Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth. Nature Cell Biology, 17(2), 170–182. https://doi.org/10.1038/ncb3090

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