c07d34fa2863d5613352eb439eb8e4f0 metabolites_a2022v12n3p243.pdf 854c06199358e60bb50a95f8a88ca3ab020c7fd6 metabolites_a2022v12n3p243.pdf adc92eb23166374d3146c69f71ea7096b5668dbfb44906115f56ce5c788e2d4d metabolites_a2022v12n3p243.pdf Title: Establishing Imaging Biomarkers of Host Immune System Efficacy during Glioblastoma Therapy Response: Challenges, Obstacles and Future Perspectives Subject: This hypothesis proposal addresses three major questions: (1) Why do we need imaging biomarkers for assessing the efficacy of immune system participation in glioblastoma therapy response? (2) Why are they not available yet? and (3) How can we produce them? We summarize the literature data supporting the claim that the immune system is behind the efficacy of most successful glioblastoma therapies but, unfortunately, there are no current short-term imaging biomarkers of its activity. We also discuss how using an immunocompetent murine model of glioblastoma, allowing the cure of mice and the generation of immune memory, provides a suitable framework for glioblastoma therapy response biomarker studies. Both magnetic resonance imaging and magnetic resonance-based metabolomic data (i.e., magnetic resonance spectroscopic imaging) can provide non-invasive assessments of such a system. A predictor based in nosological images, generated from magnetic resonance spectroscopic imaging analyses and their oscillatory patterns, should be translational to clinics. We also review hurdles that may explain why such an oscillatory biomarker was not reported in previous imaging glioblastoma work. Single shot explorations that neglect short-term oscillatory behavior derived from immune system attack on tumors may mislead actual response extent detection. Finally, we consider improvements required to properly predict immune system-mediated early response (1–2 weeks) to therapy. The sensible use of improved biomarkers may enable translatable evidence-based therapeutic protocols, with the possibility of extending preclinical results to human patients. Keywords: glioblastoma; cancer immune cycle; immunotherapy; host immune system; magnetic resonance spectroscopic imaging; metabolomics; imaging biomarker Author: Ana Paula Candiota and Carles Arús Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Mar 16 06:45:09 2022 CET ModDate: Wed Mar 16 11:44:28 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 23 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1881022 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BSTQPD+VnURWPalladioL Type 1 Custom yes yes no 10 0 MHKOUW+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 JFYKTC+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 KXPHXR+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 ENLEMO+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 ZZPUEX+ArialMT Type 1C WinAnsi yes yes no 57 0 TWGUDY+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 60 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 93 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 97 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 101 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 105 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 121 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 125 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 129 0 AOPHAZ+CMSY10 Type 1 Builtin yes yes no 137 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 149 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 153 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 157 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 161 0 CKBPVA+EURM10 Type 1 Builtin yes yes no 176 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 184 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 188 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 192 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 196 0 EWDEAL+VnURWPalladioL-Italic Type 1 Custom yes yes no 223 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-05 02:34:19 CEST RepresentationInformation: metabolites_a2022v12n3p243.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-23 11:27:18 CET Size: 1881022 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 728 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Hypothesis Proposal Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Why Do We Need Imaging Biomarkers for Assessing the Efficacy of Immune System Participation in GB Therapy Response? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Why Are Such Biomarkers of Efficacy Not Yet Available? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: How Can We Produce the Needed Biomarkers? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Limitations of the Present Hypothesis Proposal Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Info: Title: Establishing Imaging Biomarkers of Host Immune System Efficacy during Glioblastoma Therapy Response: Challenges, Obstacles and Future Perspectives Author: Ana Paula Candiota and Carles Arús Subject: This hypothesis proposal addresses three major questions: (1) Why do we need imaging biomarkers for assessing the efficacy of immune system participation in glioblastoma therapy response? (2) Why are they not available yet? and (3) How can we produce them? We summarize the literature data supporting the claim that the immune system is behind the efficacy of most successful glioblastoma therapies but, unfortunately, there are no current short-term imaging biomarkers of its activity. We also discuss how using an immunocompetent murine model of glioblastoma, allowing the cure of mice and the generation of immune memory, provides a suitable framework for glioblastoma therapy response biomarker studies. Both magnetic resonance imaging and magnetic resonance-based metabolomic data (i.e., magnetic resonance spectroscopic imaging) can provide non-invasive assessments of such a system. A predictor based in nosological images, generated from magnetic resonance spectroscopic imaging analyses and their oscillatory patterns, should be translational to clinics. We also review hurdles that may explain why such an oscillatory biomarker was not reported in previous imaging glioblastoma work. Single shot explorations that neglect short-term oscillatory behavior derived from immune system attack on tumors may mislead actual response extent detection. Finally, we consider improvements required to properly predict immune system-mediated early response (1 2 weeks) to therapy. The sensible use of improved biomarkers may enable translatable evidence-based therapeutic protocols, with the possibility of extending preclinical results to human patients. 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