Oncotarget published " Low tumour-infiltrating lymphocyte density in primary and recurrent glioblastoma " which reported that immunotherapies targeting tumour-infiltrating lymphocytes that express the immune checkpoint molecule programmed cell death-1 have shown promise in preclinical glioblastoma models but have had limited success in clinical trials.
CD3+ TILs were observed in all cases, with the majority of both primary and recurrent tumours having low density of TILs present. Quantitative analysis of TILs demonstrated significantly higher CD8+ TIL density at recurrence. No difference was observed in CD3+, CD4+ and PD-1+ TIL density between primary and recurrent groups.
Dr. Paul A. Tooney from The University of Newcastle as well as The Hunter Medical Research Institute said, " Glioblastoma , the most common and aggressive brain tumour occurring in adults, accounts for ~56% of newly diagnosed central nervous system (CNS) cancers in Australia. "
Immune checkpoint inhibition with anti-PD-1 antibodies blocks PD-1/PD-L1 interactions, restoring effector T cell proliferation and function. In melanoma, response to anti-PD-1 immunotherapy has been associated with higher density of CD8+ TILs. Previous clinical trials conducted using anti-PD-1 immunotherapy in glioblastoma have demonstrated limited success. For example, the recent CheckMate 143 trial found no significant overall survival benefit in recurrent glioblastoma with anti-PD-1 when compared to the anti-angiogenic drug bevacizumab.
Another study reported similar anti-tumour activity when anti-PD-1 plus bevacizumab was compared to bevacizumab alone. However, a recent study by Cloughesy et al found that anti-PD-1 therapy given before and after recurrent tumour resection was associated with significant increases in overall survival compared to anti-PD-1 therapy given only after recurrent surgery.
The Tooney Research Team concluded in their Oncotarget Research Output , " the level of T cell infiltration seen in this small cohort of matched primary and recurrent glioblastoma tissue was low. Though the number of CD8+ TILs was significantly higher in recurrent compared to primary tumours, overall TIL density at recurrence was still mild. PD-1+ TILs in particular were absent in the majority of our cases. Whether this is why many clinical trials using anti-PD-1 immunotherapy have not shown significant survival benefit in glioblastoma requires further investigation ."
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DOI - https://doi.org/10.18632/oncotarget.28069
Full text - https://www.oncotarget.com/article/28069/text/
Correspondence to - Paul A. Tooney - Paul.Tooney@newcastle.edu.au
Keywords - glioblastoma , tumour-infiltrating lymphocytes , programmed cell death 1 , tumour recurrence , immune microenvironment
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Oncotarget
Low tumour-infiltrating lymphocyte density in primary and recurrent glioblastoma