Oncotarget: Low tumour-infiltrating lymphocyte density in glioblastoma

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."

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.

Figure 3: Quantitative TIL scores in primary and recurrent glioblastoma. Density of CD3+, CD8+, CD4+ and PD-1+ TILs was calculated for each case and compared between primary and recurrent groups. No difference was seen in overall CD3+ TIL density (p = 0.191; A) CD8+ TILs were present at significantly higher density in recurrent tumours compared to primary tumours (p = 0.040; B). No differences were seen in CD4+ TIL density (p = 0.607; C) or PD-1+ TIL density (p = 0.070; D). Bars represent median score. PRIM: primary tumour, REC: recurrent tumour.

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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