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Journal of Experimental & Clinical Cancer Research

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01-12-2021 | Glioblastoma | Review

A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy

Authors: Jorrit De Waele, Tias Verhezen, Sanne van der Heijden, Zwi N. Berneman, Marc Peeters, Filip Lardon, An Wouters, Evelien L. J. M. Smits

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological complexities surrounding glioblastoma, lymphocytes that infiltrate the brain to develop durable immunity with memory will be key. Polyinosinic:polycytidylic acid, or poly(I:C), and its derivative poly-ICLC could serve as a priming or boosting therapy to unleash lymphocytes and other factors in the (immuno)therapeutic armory against glioblastoma. Here, we present a systematic review on the effects and efficacy of poly(I:C)/poly-ICLC for glioblastoma treatment, ranging from preclinical work on cellular and murine glioblastoma models to reported and ongoing clinical studies. MEDLINE was searched until 15 May 2021 to identify preclinical (glioblastoma cells, murine models) and clinical studies that investigated poly(I:C) or poly-ICLC in glioblastoma. A systematic review approach was conducted according to PRISMA guidelines. ClinicalTrials.gov was queried for ongoing clinical studies. Direct pro-tumorigenic effects of poly(I:C) on glioblastoma cells have not been described. On the contrary, poly(I:C) changes the immunological profile of glioblastoma cells and can also kill them directly. In murine glioblastoma models, poly(I:C) has shown therapeutic relevance as an adjuvant therapy to several treatment modalities, including vaccination and immune checkpoint blockade. Clinically, mostly as an adjuvant to dendritic cell or peptide vaccines, poly-ICLC has been demonstrated to be safe and capable of eliciting immunological activity to boost therapeutic responses. Poly-ICLC could be a valuable tool to enhance immunotherapeutic approaches for glioblastoma. We conclude by proposing several promising combination strategies that might advance glioblastoma immunotherapy and discuss key pre-clinical aspects to improve clinical translation.

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. https://doi.org/10.1056/NEJMoa043330.CrossRefPubMed

Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013–2017. Neuro Oncol. 2020;22(12 Suppl 2):iv1–iv96.CrossRefPubMedPubMedCentral

Gramatzki D, Roth P, Rushing EJ, Weller J, Andratschke N, Hofer S, et al. Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. Ann Oncol. 2018;29(6):1431–6. https://doi.org/10.1093/annonc/mdy106.CrossRefPubMed

Lim M, Xia Y, Bettegowda C, Weller M. Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol. 2018;15(7):422–42. https://doi.org/10.1038/s41571-018-0003-5.CrossRefPubMed

Chamberlin MJ, Patterson DL. Physical and chemical characterization of the ordered complexes formed between Polyinosinic acid, Polycytidylic acid and their Deoxyribo-analogues. J Mol Biol. 1965;12(2):410–28. https://doi.org/10.1016/S0022-2836(65)80264-9.CrossRefPubMed

Yu M, Levine SJ. Toll-like receptor, RIG-I-like receptors and the NLRP3 inflammasome: key modulators of innate immune responses to double-stranded RNA viruses. Cytokine Growth Factor Rev. 2011;22(2):63–72. https://doi.org/10.1016/j.cytogfr.2011.02.001.CrossRefPubMedPubMedCentral

Desmet CJ, Ishii KJ. Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol. 2012;12(7):479–91. https://doi.org/10.1038/nri3247.CrossRefPubMed

Kawai T, Akira S. Toll-like receptor and RIG-I-like receptor signaling. Ann N Y Acad Sci. 2008;1143(1):1–20. https://doi.org/10.1196/annals.1443.020.CrossRefPubMed

Sultan H, Wu J, Kumai T, Salazar AM, Celis E. Role of MDA5 and interferon-I in dendritic cells for T cell expansion by anti-tumor peptide vaccines in mice. Cancer Immunol Immunother. 2018;67(7):1091–103. https://doi.org/10.1007/s00262-018-2164-6.CrossRefPubMedPubMedCentral

10.

Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, et al. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med. 2008;205(7):1601–10. https://doi.org/10.1084/jem.20080091.CrossRefPubMedPubMedCentral

11.

Zou J, Kawai T, Tsuchida T, Kozaki T, Tanaka H, Shin KS, et al. Poly IC triggers a cathepsin D- and IPS-1-dependent pathway to enhance cytokine production and mediate dendritic cell necroptosis. Immunity. 2013;38(4):717–28. https://doi.org/10.1016/j.immuni.2012.12.007.CrossRefPubMed

12.

Ammi R, De Waele J, Willemen Y, Van Brussel I, Schrijvers DM, Lion E, et al. Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. Pharmacol Ther. 2015;146:120–31. https://doi.org/10.1016/j.pharmthera.2014.09.010.CrossRefPubMed

13.

Fucikova J, Rozkova D, Ulcova H, Budinsky V, Sochorova K, Pokorna K, et al. Poly I: C-activated dendritic cells that were generated in CellGro for use in cancer immunotherapy trials. J Transl Med. 2011;9(1):223. https://doi.org/10.1186/1479-5876-9-223.CrossRefPubMedPubMedCentral

14.

Gutcher I, Becher B. APC-derived cytokines and T cell polarization in autoimmune inflammation. J Clin Invest. 2007;117(5):1119–27. https://doi.org/10.1172/JCI31720.CrossRefPubMedPubMedCentral

15.

Moller I, Michel K, Frech N, Burger M, Pfeifer D, Frommolt P, et al. Dendritic cell maturation with poly(I:C)-based versus PGE2-based cytokine combinations results in differential functional characteristics relevant to clinical application. J Immunother (Hagerstown, Md : 1997). 2008;31(5):506–19.

16.

Cho HI, Celis E. Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects. Cancer Res. 2009;69(23):9012–9. https://doi.org/10.1158/0008-5472.CAN-09-2019.CrossRefPubMedPubMedCentral

17.

Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, et al. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med. 2009;206(7):1589–602. https://doi.org/10.1084/jem.20090247.CrossRefPubMedPubMedCentral

18.

Gerosa F, Gobbi A, Zorzi P, Burg S, Briere F, Carra G, et al. The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions. J Immunol (Baltimore, Md : 1950). 2005;174(2):727–34.CrossRef

19.

Akazawa T, Ebihara T, Okuno M, Okuda Y, Shingai M, Tsujimura K, et al. Antitumor NK activation induced by the toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells. Proc Natl Acad Sci U S A. 2007;104(1):252–7. https://doi.org/10.1073/pnas.0605978104.CrossRefPubMed

20.

Pisegna S, Pirozzi G, Piccoli M, Frati L, Santoni A, Palmieri G. p38 MAPK activation controls the TLR3-mediated up-regulation of cytotoxicity and cytokine production in human NK cells. Blood. 2004;104(13):4157–64. https://doi.org/10.1182/blood-2004-05-1860.CrossRefPubMed

21.

Maeda A, Digifico E, Andon FT, Mantovani A, Allavena P. Poly(I:C) stimulation is superior than Imiquimod to induce the antitumoral functional profile of tumor-conditioned macrophages. Eur J Immunol. 2019;49(5):801–11. https://doi.org/10.1002/eji.201847888.CrossRefPubMedPubMedCentral

22.

Rose M, Duhamel M, Aboulouard S, Kobeissy F, Tierny D, Fournier I, et al. Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by poly (I:C)-stimulated macrophages. Cancer Gene Ther. 2021. https://doi.org/10.1038/s41417-020-00286-1.

23.

Kees T, Lohr J, Noack J, Mora R, Gdynia G, Todt G, et al. Microglia isolated from patients with glioma gain antitumor activities on poly (I:C) stimulation. Neuro Oncol. 2012;14(1):64–78. https://doi.org/10.1093/neuonc/nor182.CrossRefPubMed

24.

Chen YB, Seo SY, Kirsch DG, Sheu TT, Cheng WC, Hardwick JM. Alternate functions of viral regulators of cell death. Cell Death Differ. 2006;13(8):1318–24. https://doi.org/10.1038/sj.cdd.4401964.CrossRefPubMed

25.

Feng Y, Chen Y, Meng Y, Cao Q, Liu Q, Ling C, et al. Bufalin suppresses migration and invasion of hepatocellular carcinoma cells elicited by poly (I:C) therapy. Oncoimmunology. 2018;7(5):e1426434. https://doi.org/10.1080/2162402X.2018.1426434.CrossRefPubMedPubMedCentral

26.

Matijevic Glavan T, Cipak Gasparovic A, Verillaud B, Busson P, Pavelic J. Toll-like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF. Mol Carcinog. 2017;56(4):1214–26. https://doi.org/10.1002/mc.22584.CrossRefPubMed

27.

Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. https://doi.org/10.1136/bmj.b2535.CrossRefPubMedPubMedCentral

28.

Bucur N, Mizuno M, Wakabayashi T, Yoshida J. Growth inhibition of experimental glioma by human interferon-beta superinduced by cationic liposomes entrapping polyinosilic:polycytidilic acid. Neurol Med Chir. 1998;38(8):469–73; discussion 73-4. https://doi.org/10.2176/nmc.38.469.CrossRef

29.

Carpenter S, Wochal P, Dunne A, O'Neill LA. Toll-like receptor 3 (TLR3) signaling requires TLR4 interactor with leucine-rich REPeats (TRIL). J Biol Chem. 2011;286(44):38795–804. https://doi.org/10.1074/jbc.M111.255893.CrossRefPubMedPubMedCentral

30.

De Waele J, Marcq E, Van Audenaerde JR, Van Loenhout J, Deben C, Zwaenepoel K, et al. Poly(I:C) primes primary human glioblastoma cells for an immune response invigorated by PD-L1 blockade. Oncoimmunology. 2018;7(3):e1407899. https://doi.org/10.1080/2162402X.2017.1407899.CrossRefPubMed

31.

Glas M, Coch C, Trageser D, Dassler J, Simon M, Koch P, et al. Targeting the cytosolic innate immune receptors RIG-I and MDA5 effectively counteracts cancer cell heterogeneity in glioblastoma. Stem Cells. 2013;31(6):1064–74. https://doi.org/10.1002/stem.1350.CrossRefPubMed

32.

Imaizumi T, Numata A, Yano C, Yoshida H, Meng P, Hayakari R, et al. ISG54 and ISG56 are induced by TLR3 signaling in U373MG human astrocytoma cells: possible involvement in CXCL10 expression. Neurosci Res. 2014;84:34–42. https://doi.org/10.1016/j.neures.2014.03.001.CrossRefPubMed

33.

Imaizumi T, Sakashita N, Mushiga Y, Yoshida H, Hayakari R, Xing F, et al. Desferrioxamine, an iron chelator, inhibits CXCL10 expression induced by polyinosinic-polycytidylic acid in U373MG human astrocytoma cells. Neurosci Res. 2015;94:10–6. https://doi.org/10.1016/j.neures.2015.01.001.CrossRefPubMed

34.

Imaizumi T, Yoshida H, Hayakari R, Xing F, Wang L, Matsumiya T, et al. Interferon-stimulated gene (ISG) 60, as well as ISG56 and ISG54, positively regulates TLR3/IFN-beta/STAT1 axis in U373MG human astrocytoma cells. Neurosci Res. 2016;105:35–41. https://doi.org/10.1016/j.neures.2015.09.002.CrossRefPubMed

35.

Osawa H, Mizuno M, Hatano M, Nakahara N, Tsuno T, Kuno T, et al. Susceptibility to exogenously added interferon-beta protein depends on intracellular interferon-beta mRNA level in human glioma cells. Cytokine. 2005;32(5):240–5. https://doi.org/10.1016/j.cyto.2005.10.003.CrossRefPubMed

36.

Park KC, Shimizu K, Hayakawa T. Interferon yield and MHC antigen expression of human medulloblastoma cells and its suppression during dibutyryl cyclic AMP-induced differentiation: do medulloblastoma cells derive from bipotent neuronal and glial progenitors? Cell Mol Neurobiol. 1998;18(5):497–507. https://doi.org/10.1023/A:1026327309345.CrossRefPubMed

37.

Shirai K, Shimada T, Yoshida H, Hayakari R, Matsumiya T, Tanji K, et al. Interferon (IFN)-induced protein 35 (IFI35) negatively regulates IFN-beta-phosphorylated STAT1-RIG-I-CXCL10/CCL5 axis in U373MG astrocytoma cells treated with polyinosinic-polycytidylic acid. Brain Res. 2017;1658:60–7.CrossRefPubMed

38.

Yoshida H, Imaizumi T, Matsumiya T, Seya K, Kawaguchi S, Tanaka H. Gnetin C suppresses double-stranded RNA-induced C-C motif chemokine ligand 2 (CCL2) and CCL5 production by inhibiting Toll-like receptor 3 signaling pathway. Biomed Res (Tokyo, Japan). 2018;39(5):231–40.CrossRef

39.

Zhu X, Nishimura F, Sasaki K, Fujita M, Dusak JE, Eguchi J, et al. Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models. J Transl Med. 2007;5(1):10. https://doi.org/10.1186/1479-5876-5-10.CrossRefPubMedPubMedCentral

40.

Yin P, Li H, Ke C, Cao G, Xin X, Hu J, et al. Intranasal delivery of immunotherapeutic Nanoformulations for treatment of glioma through in situ activation of immune response. Int J Nanomedicine. 2020;15:1499–515. https://doi.org/10.2147/IJN.S240551.CrossRefPubMedPubMedCentral

41.

Chacko MS, Ma X, Adamo ML. Double-stranded ribonucleic acid decreases c6 rat glioma cell proliferation in part by activating protein kinase R and decreasing insulin-like growth factor I levels. Endocrinology. 2002;143(6):2144–54. https://doi.org/10.1210/endo.143.6.8835.CrossRefPubMed

42.

Wollmann G, Robek MD, van den Pol AN. Variable deficiencies in the interferon response enhance susceptibility to vesicular stomatitis virus oncolytic actions in glioblastoma cells but not in normal human glial cells. J Virol. 2007;81(3):1479–91. https://doi.org/10.1128/JVI.01861-06.CrossRefPubMed

43.

Ghali M, Schneider-Schaulies J. Receptor (CD46)- and replication-mediated interleukin-6 induction by measles virus in human astrocytoma cells. J Neurovirol. 1998;4(5):521–30. https://doi.org/10.3109/13550289809113496.CrossRefPubMed

44.

Grauer OM, Molling JW, Bennink E, Toonen LW, Sutmuller RP, Nierkens S, et al. TLR ligands in the local treatment of established intracerebral murine gliomas. J Immunol (Baltimore, Md : 1950). 2008;181(10):6720–9.CrossRef

45.

Lee K, Kim SJ, Kim D, Jo SH, Joong Lee S, Choi SY. Prostaglandin modulates TLR3-induced cytokine expression in human astroglioma cells. Brain Res. 2014;1589:54–60. https://doi.org/10.1016/j.brainres.2014.06.036.CrossRefPubMed

46.

Tarassishin L, Casper D, Lee SC. Aberrant expression of interleukin-1beta and inflammasome activation in human malignant gliomas. PLoS One. 2014;9(7):e103432. https://doi.org/10.1371/journal.pone.0103432.CrossRefPubMedPubMedCentral

47.

Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10. https://doi.org/10.1016/j.immuni.2013.07.012.CrossRefPubMed

48.

Dhib-Jalbut SS, Xia Q, Drew PD, Swoveland PT. Differential up-regulation of HLA class I molecules on neuronal and glial cell lines by virus infection correlates with differential induction of IFN-beta. J Immunol (Baltimore, Md : 1950). 1995;155(4):2096–108.

49.

He Y, Tian Z. NK cell education via nonclassical MHC and non-MHC ligands. Cell Mol Immunol. 2017;14(4):321–30. https://doi.org/10.1038/cmi.2016.26.CrossRefPubMed

50.

Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–5. https://doi.org/10.1126/science.aar4060.CrossRefPubMedPubMedCentral

51.

Geletneky K, Hajda J, Angelova AL, Leuchs B, Capper D, Bartsch AJ, et al. Oncolytic H-1 parvovirus shows safety and signs of immunogenic activity in a first phase I/IIa glioblastoma trial. Mol Ther. 2017;25(12):2620–34. https://doi.org/10.1016/j.ymthe.2017.08.016.CrossRefPubMedPubMedCentral

52.

Alain T, Kim TS, Lun X, Liacini A, Schiff LA, Senger DL, et al. Proteolytic disassembly is a critical determinant for reovirus oncolysis. Mol Ther. 2007;15(8):1512–21. https://doi.org/10.1038/sj.mt.6300207.CrossRefPubMed

53.

Dick RS, Hubbell HR. Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations. J Neuro-Oncol. 1987;5(4):331–8. https://doi.org/10.1007/BF00148390.CrossRef

54.

Schaffert D, Kiss M, Rodl W, Shir A, Levitzki A, Ogris M, et al. Poly(I:C)-mediated tumor growth suppression in EGF-receptor overexpressing tumors using EGF-polyethylene glycol-linear polyethylenimine as carrier. Pharm Res. 2011;28(4):731–41. https://doi.org/10.1007/s11095-010-0225-4.CrossRefPubMed

55.

Shir A, Ogris M, Wagner E, Levitzki A. EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice. PLoS Med. 2006;3(1):e6. https://doi.org/10.1371/journal.pmed.0030006.CrossRefPubMed

56.

Chacko MS, Adamo ML. Double-stranded ribonucleic acid decreases C6 rat glioma cell numbers: effects on insulin-like growth factor I gene expression and action. Endocrinology. 2000;141(10):3546–55. https://doi.org/10.1210/endo.141.10.7729.CrossRefPubMed

57.

Chacko MS, Adamo ML. Double-stranded RNA decreases IGF-I gene expression in a protein kinase R-dependent, but type I interferon-independent, mechanism in C6 rat glioma cells. Endocrinology. 2002;143(2):525–34. https://doi.org/10.1210/endo.143.2.8628.CrossRefPubMed

58.

Beug ST, Beauregard CE, Healy C, Sanda T, St-Jean M, Chabot J, et al. Smac mimetics synergize with immune checkpoint inhibitors to promote tumour immunity against glioblastoma. Nat Commun. 2017;8(1). https://doi.org/10.1038/ncomms14278.

59.

Garzon-Muvdi T, Theodros D, Luksik AS, Maxwell R, Kim E, Jackson CM, et al. Dendritic cell activation enhances anti-PD-1 mediated immunotherapy against glioblastoma. Oncotarget. 2018;9(29):20681–97. https://doi.org/10.18632/oncotarget.25061.CrossRefPubMedPubMedCentral

60.

Zhu X, Fallert-Junecko BA, Fujita M, Ueda R, Kohanbash G, Kastenhuber ER, et al. Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent manners. Cancer Immunol Immunother. 2010;59(9):1401–9. https://doi.org/10.1007/s00262-010-0876-3.CrossRefPubMedPubMedCentral

61.

Zhu X, Fujita M, Snyder LA, Okada H. Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy. J Neuro-Oncol. 2011;104(1):83–92. https://doi.org/10.1007/s11060-010-0473-5.CrossRef

62.

Ohlfest JR, Andersen BM, Litterman AJ, Xia J, Pennell CA, Swier LE, et al. Vaccine injection site matters: qualitative and quantitative defects in CD8 T cells primed as a function of proximity to the tumor in a murine glioma model. Journal of immunology (Baltimore, Md : 1950). 2013;190(2):613–20.CrossRef

63.

Butowski N, Chang SM, Junck L, DeAngelis LM, Abrey L, Fink K, et al. A phase II clinical trial of poly-ICLC with radiation for adult patients with newly diagnosed supratentorial glioblastoma: a north American brain tumor consortium (NABTC01-05). J Neuro-Oncol. 2009;91(2):175–82. https://doi.org/10.1007/s11060-008-9693-3.CrossRef

64.

Hartman LL, Crawford JR, Makale MT, Milburn M, Joshi S, Salazar AM, et al. Pediatric phase II trials of poly-ICLC in the management of newly diagnosed and recurrent brain tumors. J Pediatr Hematol Oncol. 2014;36(6):451–7. https://doi.org/10.1097/MPH.0000000000000047.CrossRefPubMedPubMedCentral

65.

Rosenfeld MR, Chamberlain MC, Grossman SA, Peereboom DM, Lesser GJ, Batchelor TT, et al. A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma. Neuro-oncology. 2010;12(10):1071–7. https://doi.org/10.1093/neuonc/noq071.CrossRefPubMedPubMedCentral

66.

Salazar AM, Levy HB, Ondra S, Kende M, Scherokman B, Brown D, et al. Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study. Neurosurgery. 1996;38(6):1096–103; discussion 103-4. https://doi.org/10.1227/00006123-199606000-00006.CrossRefPubMed

67.

Boydell E, Marinari E, Migliorini D, Dietrich PY, Patrikidou A, Dutoit V. Exploratory Study of the Effect of IMA950/Poly-ICLC Vaccination on Response to Bevacizumab in Relapsing High-Grade Glioma Patients. Cancers. 2019;11(4):464. https://doi.org/10.3390/cancers11040464.

68.

Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanovic S, Gouttefangeas C, et al. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 2019;565(7738):240–5. https://doi.org/10.1038/s41586-018-0810-y.CrossRefPubMed

69.

Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019;565(7738):234–9. https://doi.org/10.1038/s41586-018-0792-9.CrossRefPubMed

70.

Migliorini D, Dutoit V, Allard M, Hallez NG, Marinari E, Widmer V, et al. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Neuro Oncol. 2019;21(7):923–33. https://doi.org/10.1093/neuonc/noz040.CrossRefPubMedPubMedCentral

71.

Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011;29(3):330–6. https://doi.org/10.1200/JCO.2010.30.7744.CrossRefPubMed

72.

Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Normolle DP, et al. Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot study. J Neuro-Oncol. 2016;130(3):517–27. https://doi.org/10.1007/s11060-016-2245-3.CrossRef

73.

Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Potter DM, et al. Antigen-specific immune responses and clinical outcome after vaccination with glioma-associated antigen peptides and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in children with newly diagnosed malignant brainstem and nonbrainstem gliomas. J Clin Oncol. 2014;32(19):2050–8. https://doi.org/10.1200/JCO.2013.54.0526.CrossRefPubMedPubMedCentral

74.

Prins RM, Soto H, Konkankit V, Odesa SK, Eskin A, Yong WH, et al. Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res. 2011;17(6):1603–15. https://doi.org/10.1158/1078-0432.CCR-10-2563.CrossRefPubMed

75.

Wang QT, Nie Y, Sun SN, Lin T, Han RJ, Jiang J, et al. Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients. Cancer Immunol Immunother. 2020;69(7):1375–87. https://doi.org/10.1007/s00262-020-02496-w.CrossRefPubMed

76.

Peereboom D, Nabors LB, Kumthekar P, Badruddoja M, Fink K, Lieberman F, et al. Results of phase 2 trial of SL-701, a novel immunotherapy targeting IL-13Ra2, EphA2, and survivin, in adults with second-line recurrent glioblastoma (GBM). Ann Oncol. 2018;29(suppl_8):viii122–viii3.CrossRef

77.

Aznar MA, Planelles L, Perez-Olivares M, Molina C, Garasa S, Etxeberria I, et al. Immunotherapeutic effects of intratumoral nanoplexed poly I:C. J Immunother Cancer. 2019;7(1):116. https://doi.org/10.1186/s40425-019-0568-2.CrossRefPubMedPubMedCentral

78.

Takeda Y, Kataoka K, Yamagishi J, Ogawa S, Seya T, Matsumoto M. A TLR3-specific adjuvant relieves innate resistance to PD-L1 blockade without cytokine toxicity in tumor vaccine immunotherapy. Cell Rep. 2017;19(9):1874–87. https://doi.org/10.1016/j.celrep.2017.05.015.CrossRefPubMed

79.

Doucette T, Rao G, Rao A, Shen L, Aldape K, Wei J, et al. Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas. Cancer Immunol Res. 2013;1(2):112–22. https://doi.org/10.1158/2326-6066.CIR-13-0028.CrossRefPubMed

80.

House IG, Savas P, Lai J, Chen AXY, Oliver AJ, Teo ZL, et al. Macrophage-derived CXCL9 and CXCL10 are required for antitumor immune responses following immune checkpoint blockade. Clin Cancer Res. 2020;26(2):487–504. https://doi.org/10.1158/1078-0432.CCR-19-1868.CrossRefPubMed

81.

Bald T, Landsberg J, Lopez-Ramos D, Renn M, Glodde N, Jansen P, et al. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov. 2014;4(6):674–87. https://doi.org/10.1158/2159-8290.CD-13-0458.CrossRefPubMed

82.

Hussain RZ, Cravens PC, Doelger R, Dentel B, Herndon E, Loof N, et al. TLR3 agonism re-establishes CNS immune competence during alpha4-integrin deficiency. Ann Clin Transl Neurol. 2018;5(12):1543–61. https://doi.org/10.1002/acn3.664.CrossRefPubMedPubMedCentral

83.

Zemek RM, De Jong E, Chin WL, Schuster IS, Fear VS, Casey TH, et al. Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironment. Sci Transl Med. 2019;11(501):eaav7816. https://doi.org/10.1126/scitranslmed.aav7816.

84.

Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med. 2003;9(5):562–7. https://doi.org/10.1038/nm863.CrossRefPubMed

85.

Lee YS, O'Brien LJ, Walpole CM, Pearson FE, Leal-Rojas IM, Masterman KA, et al. Human CD141(+) dendritic cells (cDC1) are impaired in patients with advanced melanoma but can be targeted to enhance anti-PD-1 in a humanized mouse model. J Immunother Cancer. 2021;9(3):e001963. https://doi.org/10.1136/jitc-2020-001963.

86.

Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019;25(3):477–86. https://doi.org/10.1038/s41591-018-0337-7.CrossRefPubMedPubMedCentral

87.

Cockle JV, Rajani K, Zaidi S, Kottke T, Thompson J, Diaz RM, et al. Combination viroimmunotherapy with checkpoint inhibition to treat glioma, based on location-specific tumor profiling. Neuro-oncology. 2016;18(4):518–27. https://doi.org/10.1093/neuonc/nov173.CrossRefPubMed

88.

Graeber MB, Scheithauer BW, Kreutzberg GW. Microglia in brain tumors. Glia. 2002;40(2):252–9. https://doi.org/10.1002/glia.10147.CrossRefPubMed

89.

Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013;19(10):1264–72. https://doi.org/10.1038/nm.3337.CrossRefPubMedPubMedCentral

90.

Shime H, Matsumoto M, Oshiumi H, Tanaka S, Nakane A, Iwakura Y, et al. Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors. Proc Natl Acad Sci U S A. 2012;109(6):2066–71. https://doi.org/10.1073/pnas.1113099109.CrossRefPubMedPubMedCentral

91.

Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003. https://doi.org/10.1056/NEJMoa043331.CrossRefPubMed

92.

Natsume A, Wakabayashi T, Ishii D, Maruta H, Fujii M, Shimato S, et al. A combination of IFN-beta and temozolomide in human glioma xenograft models: implication of p53-mediated MGMT downregulation. Cancer Chemother Pharmacol. 2008;61(4):653–9. https://doi.org/10.1007/s00280-007-0520-x.CrossRefPubMed

93.

Wakabayashi T, Natsume A, Mizusawa J, Katayama H, Fukuda H, Sumi M, et al. JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonbeta plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma. J Neuro-Oncol. 2018;138(3):627–36. https://doi.org/10.1007/s11060-018-2831-7.CrossRef

94.

Brown NF, Carter TJ, Ottaviani D, Mulholland P. Harnessing the immune system in glioblastoma. Br J Cancer. 2018;119(10):1171–81. https://doi.org/10.1038/s41416-018-0258-8.CrossRefPubMedPubMedCentral

95.

Chiang CS, Fu SY, Wang SC, Yu CF, Chen FH, Lin CM, et al. Irradiation promotes an m2 macrophage phenotype in tumor hypoxia. Front Oncol. 2012;2:89.CrossRefPubMedPubMedCentral

96.

Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2011–2015. Neuro Oncol. 2018;20(suppl_4):iv1–iv86.CrossRefPubMedPubMedCentral

97.

De Waele J, Reekmans K, Daans J, Goossens H, Berneman Z, Ponsaerts P. 3D culture of murine neural stem cells on decellularized mouse brain sections. Biomaterials. 2015;41:122–31. https://doi.org/10.1016/j.biomaterials.2014.11.025.CrossRefPubMed

98.

Akins EA, Aghi MK, Kumar S. Incorporating Tumor-Associated Macrophages into Engineered Models of Glioma. iScience. 2020;23(12):101770.CrossRefPubMedPubMedCentral

99.

Hubert CG, Rivera M, Spangler LC, Wu Q, Mack SC, Prager BC, et al. A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and Cancer stem cell heterogeneity of tumors found in vivo. Cancer Res. 2016;76(8):2465–77. https://doi.org/10.1158/0008-5472.CAN-15-2402.CrossRefPubMedPubMedCentral

100.

Jacob F, Salinas RD, Zhang DY, Nguyen PTT, Schnoll JG, Wong SZH, et al. A patient-derived glioblastoma organoid model and biobank recapitulates inter- and intra-tumoral heterogeneity. Cell. 2020;180(1):188–204 e22. https://doi.org/10.1016/j.cell.2019.11.036.CrossRefPubMed

101.

Linkous A, Balamatsias D, Snuderl M, Edwards L, Miyaguchi K, Milner T, et al. Modeling patient-derived glioblastoma with cerebral organoids. Cell Rep. 2019;26(12):3203–11 e5. https://doi.org/10.1016/j.celrep.2019.02.063.CrossRefPubMedPubMedCentral

102.

Yi HG, Jeong YH, Kim Y, Choi YJ, Moon HE, Park SH, et al. A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy. Nat Biomed Eng. 2019;3(7):509–19. https://doi.org/10.1038/s41551-019-0363-x.CrossRefPubMed

103.

Miyai M, Tomita H, Soeda A, Yano H, Iwama T, Hara A. Current trends in mouse models of glioblastoma. J Neuro-Oncol. 2017;135(3):423–32. https://doi.org/10.1007/s11060-017-2626-2.CrossRef

104.

Wouters R, Bevers S, Riva M, De Smet F, Coosemans A. Immunocompetent Mouse Models in the Search for Effective Immunotherapy in Glioblastoma. Cancers. 2020;13(1):19. https://doi.org/10.3390/cancers13010019.

105.

Iorgulescu JB, Gokhale PC, Speranza MC, Eschle BK, Poitras MJ, Wilkens MK, et al. Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma. Clin Cancer Res. 2020;21(1):276–87. https://doi.org/10.1158/1078-0432.CCR-20-2291.

Title: A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy
Authors: Jorrit De Waele
Tias Verhezen
Sanne van der Heijden
Zwi N. Berneman
Marc Peeters
Filip Lardon
An Wouters
Evelien L. J. M. Smits
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Glioblastoma
Glioma
Vaccination
Glioma
Glioblastoma
Glioblastoma
Glioma
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-02017-2

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