- Title
- Low tumour-infiltrating lymphocyte density in primary and recurrent glioblastoma
- Creator
- Maddison, Kelsey; Graves, Moira C.; Bowden, Nikola A.; Fay, Michael; Vilain, Ricardo E.; Faulkner, Sam; Tooney, Paul A.
- Relation
- Oncotarget Vol. 12, Issue 21, p. 2177-2187
- Publisher Link
- http://dx.doi.org/10.18632/ONCOTARGET.28069
- Publisher
- Impact Journals LLC
- Resource Type
- journal article
- Date
- 2021
- Description
- Immunotherapies targeting tumour-infiltrating lymphocytes (TILs) that express the immune checkpoint molecule programmed cell death-1 (PD-1) have shown promise in preclinical glioblastoma models but have had limited success in clinical trials. To assess when glioblastoma is most likely to benefit from immune checkpoint inhibitors we determined the density of TILs in primary and recurrent glioblastoma. Thirteen cases of matched primary and recurrent glioblastoma tissue were immunohistochemically labelled for CD3, CD8, CD4 and PD-1, and TIL density assessed. CD3+ TILs were observed in all cases, with the majority of both primary (69.2%) and recurrent (61.5%) tumours having low density of TILs present. CD8+ TILs were observed at higher densities than CD4+ TILs in both tumour groups. PD-1+ TILs were sparse and present in only 25% of primary and 50% of recurrent tumours. Quantitative analysis of TILs demonstrated significantly higher CD8+ TIL density at recurrence (p = 0.040). No difference was observed in CD3+ (p = 0.191), CD4+ (p = 0.607) and PD-1+ (p = 0.070) TIL density between primary and recurrent groups. This study shows that TILs are present at low densities in both primary and recurrent glioblastoma. Furthermore, PD-1+ TILs were frequently absent, which may provide evidence as to why anti-PD-1 immunotherapy trials have been largely unsuccessful in glioblastoma.
- Subject
- glioblastoma; tumour-infiltrating lymphocytes; programmed cell death 1; tumour recurrence; immune microenvironment; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1472704
- Identifier
- uon:48900
- Identifier
- ISSN:1949-2553
- Rights
- © 2021 Maddison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Language
- eng
- Full Text
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