This preprint is under consideration at Journal of Neuro-Oncology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research Article
David Alexander Cieremans
Columbia University Irving Medical Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1809-4733
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Introduction: PD-1 inhibitors have shown limited efficacy in glioblastoma due to microenvironment immunosuppression and low tumor mutational burden. In GBM, PD-L1 expression is not a predictive marker for response to PD-1 or PD-L1 inhibitors. Multiplex immunostaining panel technology allows for detailed analyses of tumor microenvironment cells and their interaction.
Methods: Pre-treatment tumor tissue was collected retrospectively from 27 patients at Columbia University Irving Medical Center with primary glioblastoma who were diagnosed within the past three years, had surgery here, and were either treated with SOC therapy (n= 8) or PD-1 inhibitors at recurrence (n= 19). Multiplex immunofluorescence panels included 1) CD11b/IDO1/HLADR/GFAP, 2) PD1/PD-L1/GFAP, and 3) CD4/CD8/CD25/FoxP3/Ki67/GFAP.
Results: Multiplex immunofluorescence panels did not show any correlation with outcomes in patients treated with SOC therapy. Among the 19 patients treated with PD-1 inhibitors, those with more HLA-DR positive cells had worse outcomes (p= 0.02). PD-L1 expression on tumor cells was not predictive of outcomes. There was a correlation trend between PD-1/PD-L1 interaction score (p= 0.08) and outcomes. PTEN loss was correlated with higher Ki67 expression in both tumor cells (p= 0.05) and non-tumors cells (p= 0.03); however, this was not found in Ki67 in CD4+ cells, CD8+ cells, or CD4+CD8+ cells combined. Tumor-associated macrophages, myeloid-derived suppressor cells, CD8+ cells, and CD4+ cells were not significant predictive markers for outcome.
Conclusion: Quantitative spatial profiling by multiplex immunofluorescence is feasible in FFPE glioblastoma tissue. More refined and extensive quantitative and spatial microenvironment analyses may allow for the development of biomarkers for immunotherapy in GBM.
Keywords
glioblastoma, immunotherapy, biomarkers, tumor microenvironment
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This preprint is under consideration at Journal of Neuro-Oncology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
David Alexander Cieremans
Columbia University Irving Medical Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1809-4733
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 24 Mar, 2021
No community comments so far
Reviews received
Received 26 Mar, 2021
Reviewers invited
Invitations sent on 17 Mar, 2021
Editor assigned
On 17 Mar, 2021
First submitted
On 17 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Introduction: PD-1 inhibitors have shown limited efficacy in glioblastoma due to microenvironment immunosuppression and low tumor mutational burden. In GBM, PD-L1 expression is not a predictive marker for response to PD-1 or PD-L1 inhibitors. Multiplex immunostaining panel technology allows for detailed analyses of tumor microenvironment cells and their interaction.
Methods: Pre-treatment tumor tissue was collected retrospectively from 27 patients at Columbia University Irving Medical Center with primary glioblastoma who were diagnosed within the past three years, had surgery here, and were either treated with SOC therapy (n= 8) or PD-1 inhibitors at recurrence (n= 19). Multiplex immunofluorescence panels included 1) CD11b/IDO1/HLADR/GFAP, 2) PD1/PD-L1/GFAP, and 3) CD4/CD8/CD25/FoxP3/Ki67/GFAP.
Results: Multiplex immunofluorescence panels did not show any correlation with outcomes in patients treated with SOC therapy. Among the 19 patients treated with PD-1 inhibitors, those with more HLA-DR positive cells had worse outcomes (p= 0.02). PD-L1 expression on tumor cells was not predictive of outcomes. There was a correlation trend between PD-1/PD-L1 interaction score (p= 0.08) and outcomes. PTEN loss was correlated with higher Ki67 expression in both tumor cells (p= 0.05) and non-tumors cells (p= 0.03); however, this was not found in Ki67 in CD4+ cells, CD8+ cells, or CD4+CD8+ cells combined. Tumor-associated macrophages, myeloid-derived suppressor cells, CD8+ cells, and CD4+ cells were not significant predictive markers for outcome.
Conclusion: Quantitative spatial profiling by multiplex immunofluorescence is feasible in FFPE glioblastoma tissue. More refined and extensive quantitative and spatial microenvironment analyses may allow for the development of biomarkers for immunotherapy in GBM.
Figure 1
Figure 2
Figure 3
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