Anti-tumour immune response in GL261 glioblastoma generated by Temozolomide Immune-Enhancing Metronomic Schedule monitored with MRSI-based nosological images.
Administration, Metronomic
Animals
Antineoplastic Agents, Alkylating
/ administration & dosage
B7-H1 Antigen
/ metabolism
Cell Line, Tumor
Glioblastoma
/ diagnostic imaging
Humans
Immunologic Memory
/ drug effects
Magnetic Resonance Imaging
Mice, Inbred C57BL
Temozolomide
/ administration & dosage
Tumor Burden
/ drug effects
PD-L1
glioma
immune memory, TMZ
immune response
metronomic therapy
orthotopic tumours
Journal
NMR in biomedicine
ISSN: 1099-1492
Titre abrégé: NMR Biomed
Pays: England
ID NLM: 8915233
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
27
07
2019
revised:
25
10
2019
accepted:
30
10
2019
pubmed:
12
1
2020
medline:
8
1
2021
entrez:
12
1
2020
Statut:
ppublish
Résumé
Glioblastomas (GB) are brain tumours with poor prognosis even after aggressive therapy. Improvements in both therapeutic and follow-up strategies are urgently needed. In previous work we described an oscillatory pattern of response to Temozolomide (TMZ) using a standard administration protocol, detected through MRSI-based machine learning approaches. In the present work, we have introduced the Immune-Enhancing Metronomic Schedule (IMS) with an every 6-d TMZ administration at 60 mg/kg and investigated the consistence of such oscillatory behaviour. A total of n = 17 GL261 GB tumour-bearing C57BL/6j mice were studied with MRI/MRSI every 2 d, and the oscillatory behaviour (6.2 ± 1.5 d period from the TMZ administration day) was confirmed during response. Furthermore, IMS-TMZ produced significant improvement in mice survival (22.5 ± 3.0 d for controls vs 135.8 ± 78.2 for TMZ-treated), outperforming standard TMZ treatment. Histopathological correlation was investigated in selected tumour samples (n = 6) analyzing control and responding fields. Significant differences were found for CD3+ cells (lymphocytes, 3.3 ± 2.5 vs 4.8 ± 2.9, respectively) and Iba-1 immunostained area (microglia/macrophages, 16.8% ± 9.7% and 21.9% ± 11.4%, respectively). Unexpectedly, during IMS-TMZ treatment, tumours from some mice (n = 6) fully regressed and remained undetectable without further treatment for 1 mo. These animals were considered "cured" and a GL261 re-challenge experiment performed, with no tumour reappearance in five out of six cases. Heterogeneous therapy response outcomes were detected in tumour-bearing mice, and a selected group was investigated (n = 3 non-responders, n = 6 relapsing tumours, n = 3 controls). PD-L1 content was found ca. 3-fold increased in the relapsing group when comparing with control and non-responding groups, suggesting that increased lymphocyte inhibition could be associated to IMS-TMZ failure. Overall, data suggest that host immune response has a relevant role in therapy response/escape in GL261 tumours under IMS-TMZ therapy. This is associated to changes in the metabolomics pattern, oscillating every 6 d, in agreement with immune cycle length, which is being sampled by MRSI-derived nosological images.
Substances chimiques
Antineoplastic Agents, Alkylating
0
B7-H1 Antigen
0
Cd274 protein, mouse
0
Temozolomide
YF1K15M17Y
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4229Informations de copyright
© 2020 John Wiley & Sons, Ltd.
Références
Buckner JC. Factors influencing survival in high-grade gliomas. Semin Oncol. 2003;30:10-14.
Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459-466.
Dhermain FG, Hau P, Lanfermann H, Jacobs AH, van den Bent MJ. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol. 2010;9(9):906-920.
Vogelbaum MA, Jost S, Aghi MK, et al. Application of novel response/progression measures for surgically delivered therapies for gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group. Neurosurgery. 2012;70(1):234-243.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.
Hygino da Cruz LC, Rodriguez I, Domingues RC, Gasparetto EL, Sorensen AG. Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. Am J Neuroradiol. 2011;32(11):1978-1985.
Pichler BJ, Wehrl HF, Judenhofer MS. Latest advances in molecular imaging instrumentation. J Nucl Med. 2008;49(suppl 2):5S-23S.
Horská A, Barker PB. Imaging of brain tumors: MR spectroscopy and metabolic imaging. Neuroimaging Clin N Am. 2010;20(3):293-310.
Hattingen E, Jurcoane A, Bahr O, et al. Bevacizumab impairs oxidative energy metabolism and shows antitumoral effects in recurrent glioblastomas: a 31P/1H MRSI and quantitative magnetic resonance imaging study. Neuro Oncol. 2011;13(12):1349-1363.
Nelson SJ. Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI. NMR Biomed. 2011;24(6):734-749.
Ortega-Martorell S, Julià-Sapé M, Lisboa P, Arús C. Pattern recognition analysis of MR spectra. In: EMagRes. Vol.5 Chichester, UK: John Wiley & Sons; 2016:945-958.
Laudadio T, Martínez-Bisbal MC, Celda B, Van Huffel S. Fast nosological imaging using canonical correlation analysis of brain data obtained by two-dimensional turbo spectroscopic imaging. NMR Biomed. 2008;21(4):311-321.
Simões RV, Ortega-Martorell S, Delgado-Goñi T, et al. Improving the classification of brain tumors in mice with perturbation enhanced (PE)-MRSI. Integr Biol (Camb). 2012;4(2):183-191.
Arias-Ramos N, Ferrer-Font L, Lope-Piedrafita S, et al. Metabolomics of therapy response in preclinical glioblastoma: a multi-slice MRSI-based volumetric analysis for noninvasive assessment of temozolomide treatment. Metabolites. 2017;7(2):20.
Liikanen I, Ahtiainen L, Hirvinen ML, et al. Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients. Mol Ther. 2013;21(6):1212-1223.
Karman J, Ling C, Sandor M, Fabry Z. Initiation of immune responses in brain is promoted by local dendritic cells. J Immunol. 2004;173(4):2353-2361.
Wu J, Waxman DJ. Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8+ T-cell responses and immune memory. Oncoimmunology. 2015;4(4):e1005521.
Villamañán L. Unraveling CK2 Inhibition and Temozolomide Contribution to Therapy Response in Preclinical GL261 Gglioblastoma: Immune System Implications and Magnetic Resonance Based Nosological Imaging [disseration]. Univ Autònoma Barcelona; 2019. https://tdx.cat/handle/10803/666881.
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1-10.
Lorger M. Tumor microenvironment in the brain. Cancers (Basel). 2012;4(1):218-243.
He J, Hu Y, Hu M, Li B. Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci Rep. 2015;5(1):13110.
Katsuya Y, Horinouchi H, Asao T, et al. Expression of programmed death 1 (PD-1) and its ligand (PD-L1) in thymic epithelial tumors: impact on treatment efficacy and alteration in expression after chemotherapy. Lung Cancer. 2016;99:4-10.
Hecht M, Büttner-Herold M, Erlenbach-Wünsch K, et al. PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis. Eur J Cancer. 2016;65:52-60.
Zhang P, Su D-M, Liang M, Fu J. Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis. Mol Immunol. 2008;45(5):1470-1476.
Simões RV, Delgado-Goñi T, Lope-Piedrafita S, Arús C. 1 H-MRSI pattern perturbation in a mouse glioma: the effects of acute hyperglycemia and moderate hypothermia. NMR Biomed. 2010;23(1):23-33.
Simões RV, García-Martín ML, Cerdán S, Arús C. Perturbation of mouse glioma MRS pattern by induced acute hyperglycemia. NMR Biomed. 2008;21(3):251-264.
Ortega-Martorell S, Ruiz H, Vellido A, et al. A novel semi-supervised methodology for extracting tumor type-specific MRS sources in human brain data. Monleon D, ed. PLoS One. 2013;8(12):e83773.
Ortega-Martorell S, Lisboa PJG, Vellido A, et al. Convex non-negative matrix factorization for brain tumor delimitation from MRSI data. Monleon D, ed. PLoS One. 2012;7(10):e47824.
Delgado-Goñi T, Ortega-Martorell S, Ciezka M, et al. MRSI-based molecular imaging of therapy response to temozolomide in preclinical glioblastoma using source analysis. NMR Biomed. 2016;29(6):732-743.
Ferrer-Font L, Villamañan L, Arias-Ramos N, et al. Targeting protein kinase CK2: evaluating CX-4945 potential for GL261 glioblastoma therapy in immunocompetent mice. Pharmaceuticals. 2017;10(4):24.
Ferrer-Font L, Arias-Ramos N, Lope-Piedrafita S, et al. Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide. NMR Biomed. 2017;30(9):1-12.
Ciezka M, Acosta M, Herranz C, et al. Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation. J Neurooncol. 2016;129(1):67-76.
Karman J, Ling C, Sandor M, Fabry Z. Initiation of immune responses in brain is promoted by local dendritic cells. J Immunol. 2004;173(4):2353-2361.
Kim T-G, Kim C-H, Park J-S, et al. Immunological factors relating to the antitumor effect of temozolomide chemoimmunotherapy in a murine glioma model. Clin Vaccine Immunol. 2010;17(1):143-153.
Curtin JF, Liu N, Candolfi M, et al. HMGB1 mediates endogenous TLR2 activation and brain tumor regression. Weil R, ed. PLoS Med. 2009;6(1):e1000010.
Roesch S, Rapp C, Dettling S, Herold-Mende C. When immune cells turn bad-tumor-associated microglia/macrophages in glioma. Int J Mol Sci. 2018;19(2):436.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793-800.
Hanson HL, Donermeyer DL, Ikeda H, et al. Eradication of established tumors by CD8+ T cell adoptive immunotherapy. Immunity. 2000;13(2):265-276.
Samanta D, Park Y, Ni X, et al. Chemotherapy induces enrichment of CD47 + /CD73 +/PDL1 + immune evasive triple-negative breast cancer cells. Proc Natl Acad Sci USA. 2018;115(6):E1239-E1248.
Wu J, Jordan M, Waxman DJ. Metronomic cyclophosphamide activation of anti-tumor immunity: tumor model, mouse host, and drug schedule dependence of gene responses and their upstream regulators. BMC Cancer. 2016;16(1):623.
Schiavoni G, Sistigu A, Valentini M, et al. Cyclophosphamide synergizes with Type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res. 2011;71(3):768-778.
Dai B, Qi N, Li J, Zhang G. Temozolomide combined with PD-1 Antibody therapy for mouse orthotopic glioma model. Biochem Biophys Res Commun. 2018;501(4):871-876.
Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013;31(32):4085-4091.
Szatmári T, Lumniczky K, Désaknai S, et al. Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy. Cancer Sci. 2006;97(6):546-553.
Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197-218.