by RCSI University of Medicine and Health Sciences

Trend towards improved OS and increased response rate in TME^High patients following adjuvant treatment with pembrolizumab or PVSRIPO . A. TME composition in 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. Nat Med. March 11, 2019;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 (N=24) samples. B. OS according to TME^High and non-TME^High (TME^Low + TME^Med) subtypes who received adjuvant anti-PD1 therapy in the Zhao cohort (N=15 patients). C. Relative boxplots indicating the proportion of TME^Low, TME^Med and TME^High patients before administration of anti-PD1 treatment (left) and after anti-PD1 treatment (right) in available tumor and blood samples. D. Partition around medoids (PAM) clustering of the PVSRIPO cohort¹⁹Desjardins A. Gromeier M. Herndon J.E. Beaubier N. Bolognesi D.P. Friedman A.H. 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 TME composition described by GBM-MCP-counter scores reveal 3 subtypes; TME^low, TME ^med and TME ^high. E. OS according to TME^Low and TME^Med and TME^High subtypes who received PVSRIPO therapy in the PVSRIPO cohort¹⁹Desjardins A. Gromeier M. Herndon J.E. Beaubier N. Bolognesi D.P. Friedman A.H. 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 log-ranked test. *P<0.05 ** P<0.01. Credit: Annals of Oncology (2022). DOI: 10.1016/j.annonc.2022.11.008

Research lead by RCSI University of Medicine and Health Sciences has discovered three new subtypes of brain tumor that could help to identify new and effective therapies. The novel tumor subtypes are forms of glioblastoma, the most common and most aggressive form of adult primary brain cancer with no cure currently available.

The research, published in Annals of Oncology, has identified that glioblastoma tumors can be placed into three categories based on the different kind of non-cancer cells that can be found within the tumor. These so-called tumor microenvironment cells can include immune cells and blood vessel cells.

Currently, the majority of patients with glioblastoma are treated in the same way. Further investigation of these newly identified subtypes will mean that different patients could receive treatment specific to the cells in their own tumor. This type of targeted treatment is known as precision medicine.

Senior author and lead investigator, Professor Annette Byrne, head of the RCSI Precision Cancer Medicine Group, commented, "Glioblastoma patients currently have a poor prognosis due to limited treatment options so it is vital that new treatments be developed. Targeted treatment or precision medicine has the potential to improve outcomes for these patients. We hope 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 that have the tumor subtype defined by high levels of immune cells within their tumor microenvironment. An assessment of glioblastoma clinical trial datasets by this research group provided support for this idea, showing that patients with this subtype of tumor may have an improved outcome when treated with immunotherapies compared to other subtypes.

More information: K. White et al, Identification, validation and biological characterization of novel Glioblastoma Tumour Microenvironment subtypes: Implications for precision immunotherapy, Annals of Oncology (2022). DOI: 10.1016/j.annonc.2022.11.008

Journal information: New England Journal of Medicine  , Annals of Oncology 

Provided by RCSI University of Medicine and Health Sciences