pre- vs post-adjuvant anti-PD1 treatment in available tumor samples (N = 24). B. OS according to TMEHigh and not TMEHigh (TMEDown + TMEWith) subtypes who received adjuvant anti-PD1 therapy in the Zhao cohort (N = 15 patients). C. Relative boxplots indicating the proportion of TMEDown, TMEWith and TMEHigh patients before administration of anti-PD1 treatment (left) and after anti-PD1 treatment (right) in available tumor and blood samples. D. Grouping of the partition around the medoids (PAM) of the PVSRIPO cohort19Desjardins A. Gromeier M. Herndon JE Beaubier N. Bolognesi DP Friedman AH et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus.New England Journal of Medicine. July 12, 2018; 379: 150-161CrossrefPubMedScopus (0)Google Scholar with available RNA-seq data (N=12), based on the cellular composition of TME described by GBM-MCP-counter scores reveal 3 subtypes; TMEdownTME with and TME high. E. OS according to TMEDown and TMEWith and TMEHigh subtypes who received treatment with PVSRIPO in the PVSRIPO cohort19Desjardins A. Gromeier M. Herndon JE Beaubier N. Bolognesi DP Friedman AH et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus.New England Journal of Medicine. July 12, 2018; 379: 150-161CrossrefPubMedScopus (0)Google Scholar. Statistical test: Wilcoxon signed rank test. Kaplan Meier analysis; P value of the logarithmic test. *P<0.05 **P<0.01. Credit: Annals of Oncology (2022). DOI: 10.1016/j.annonc.2022.11.008″>
pre- vs post-adjuvant anti-PD1 treatment in available tumor samples (N = 24). B. OS according to TMEHigh and not TMEHigh (TMEDown + TMEWith) subtypes who received adjuvant anti-PD1 therapy in the Zhao cohort (N = 15 patients). C. Relative boxplots indicating the proportion of TMEDown, TMEWith and TMEHigh patients before administration of anti-PD1 treatment (left) and after anti-PD1 treatment (right) in available tumor and blood samples. D. Grouping of the partition around the medoids (PAM) of the PVSRIPO cohort19Desjardins A. Gromeier M. Herndon JE Beaubier N. Bolognesi DP Friedman AH et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus.New England Journal of Medicine. July 12, 2018; 379: 150-161CrossrefPubMedScopus (0)Google Scholar with available RNA-seq data (N=12), based on the cellular composition of TME described by GBM-MCP-counter scores reveal 3 subtypes; TMEdownTME with and TME high. E. OS according to TMEDown and TMEWith and TMEHigh subtypes who received treatment with PVSRIPO in the PVSRIPO cohort19Desjardins A. Gromeier M. Herndon JE Beaubier N. Bolognesi DP Friedman AH et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus.New England Journal of Medicine. July 12, 2018; 379: 150-161CrossrefPubMedScopus (0)Google Scholar. Statistical test: Wilcoxon signed rank test. Kaplan Meier analysis; P value of the logarithmic test. *P<0.05 **P<0.01. Credit: Annals of Oncology (2022). DOI: 10.1016/j.annonc.2022.11.008″ width=”546″ height=”530″/>
Trend of improving OS and increasing response rate in TMEHigh patients on adjuvant therapy with pembrolizumab or PVSRIPO. A. Composition of TME in the Zhao dataset18Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L, Chu T, et al. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. NatMed. 2019 Mar 11;25(3):462–469. Available at: http://www.nature.com/articles/s41591-019-0349-yGoogle Scholar pre- vs post-adjuvant anti-PD1 treatment in available tumor samples (N = 24). B. OS according to TMEHigh and not TMEHigh (TMEDown + TMEWith) subtypes who received adjuvant anti-PD1 therapy in the Zhao cohort (N = 15 patients). C. Relative boxplots indicating the proportion of TMEDown, TMEWith and TMEHigh patients before administration of anti-PD1 treatment (left) and after anti-PD1 treatment (right) in available tumor and blood samples. D. Grouping of the partition around the medoids (PAM) of the PVSRIPO cohort19Desjardins A. Gromeier M. Herndon JE Beaubier N. Bolognesi DP Friedman AH et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus.New England Journal of Medicine. July 12, 2018; 379: 150-161CrossrefPubMedScopus (0)Google Scholar with available RNA-seq data (N=12), based on the cellular composition of TME described by GBM-MCP-counter scores reveal 3 subtypes; TMEdownTME with and TME high. E. OS according to TMEDown and TMEWith and TMEHigh subtypes who received treatment with PVSRIPO in the PVSRIPO cohort19Desjardins A. Gromeier M. Herndon JE Beaubier N. Bolognesi DP Friedman AH et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus.New England Journal of Medicine. July 12, 2018; 379: 150-161CrossrefPubMedScopus (0)Google Scholar. Statistical test: Wilcoxon signed rank test. Kaplan Meier analysis; P value of the logarithmic test. *P<0.05 **P<0.01. Credit: Annals of Oncology (2022). DOI: 10.1016/j.annonc.2022.11.008
Research conducted by the University of Medicine and Health Sciences RCSI has discovered three new subtypes of brain tumors that could help identify new and effective therapies. The new tumor subtypes are forms of glioblastoma, the most common and aggressive form of primary brain cancer in adults with no currently available treatment.
The research, published in Annals of Oncology, identified that glioblastoma tumors can be classified into three categories based on the different types of non-cancerous cells that can be found in the tumor. These so-called tumor microenvironment cells can include immune cells and blood vessel cells.
Currently, the majority of glioblastoma patients are treated the same way. Further investigation of these newly identified subtypes will mean that different patients could receive treatment specific to their own tumor cells. This type of targeted treatment is known as precision medicine.
Lead author and principal investigator, Professor Annette Byrne, Head of RCSI Precision Cancer Medicine Group, said: “Patients with glioblastoma currently have a poor prognosis due to limited treatment options, so it is vital that new treatments are developed. Targeted therapy or precision medicine has the potential to improve outcomes for these patients. We hope that further analysis of the tumor subtypes identified in this research will provide the data needed to support future glioblastoma clinical trials in Ireland.
Precision medicine approaches could include the use of immune-targeting therapies (immunotherapies) in patients who have the tumor subtype defined by elevated levels of immune cells in their tumor microenvironment. An evaluation of glioblastoma clinical trial datasets by this research group supported this idea, showing that patients with this tumor subtype may have a better outcome when treated with immunotherapies compared to to other subtypes.
More information:
K. White et al, Identification, Validation, and Biological Characterization of Novel Glioblastoma Tumor Microenvironment Subtypes: Implications for Precision Immunotherapy, Annals of Oncology (2022). DOI: 10.1016/j.annonc.2022.11.008
Provided by RCSI University of Medicine and Health Sciences
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