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. 2024 Oct;50(5):e13012.
doi: 10.1111/nan.13012.

Characterisation of the tumour microenvironment in primary and recurrent glioblastomas

Arnon Møldrup Knudsen  1   2   3 , Jesper Dupont Ewald  1   2 , Vilde Pedersen  4   5 , Martin Haupt-Jorgensen  4 , Elisabeth Victoria Riber Hansen  6 , Bjarne Winther Kristensen  1   2   4   5
Affiliations

Characterisation of the tumour microenvironment in primary and recurrent glioblastomas

Arnon Møldrup Knudsen et al. Neuropathol Appl Neurobiol. 2024 Oct.

Abstract

Aims: Glioblastoma patients have a dismal prognosis, due to inevitable tumour recurrence and respond poorly to immunotherapy. Tumour-associated microglia/macrophages (TAMs) dominate the glioblastoma tumour microenvironment and have been implicated in tumour progression and immune evasion. Early recurrent glioblastomas contain focal reactive regions with occasional fibrosis, chronic inflammation, TAMs and tumour cells. Surgical specimens from these tumours are rare and provide crucial insights into glioblastoma recurrence biology. This study aimed to characterise TAM- and lymphocyte phenotypes in primary vs early- and late-recurrent glioblastomas.

Methods: Patient-matched primary and recurrent glioblastomas were compared between patients with early recurrences (n = 11, recurrence ≤6 months) and late recurrences (n = 12, recurrence after 12-19 months). Double-immunofluorescence stains combining Iba1 with HLA-DR, CD14, CD68, CD74, CD86, CD163, CD204 and CD206 along with stains for CD20, CD3, CD8 and FOXP3 were quantified with software-based classifiers.

Results: Reactive regions in early recurrent tumours contained more TAMs (31.4% vs 21.7%, P = 0.01), which showed increased expression of CD86 (59.4% vs 38.4%, P = 0.04), CD204 (48.5% vs 28.4%, P = 0.03), CD206 (25.5% vs 14.4%, P = 0.04) and increased staining intensity for CD163 (86.4 vs 57.7 arbitrary units, P = 0.02), compared to late recurring tumours. Reactive regions contained more B-lymphocytes compared to patient-matched primary tumours (0.71% vs 0.40%, P = 0.04). Fractions of total, cytotoxic and regulatory T-lymphocytes did not differ.

Conclusions: Early recurrent glioblastomas showed enrichment for TAMs, expressing both pro- and anti-inflammatory markers and B-lymphocytes. This may indicate a time-dependent response to immunotherapy explained by time-dependent alterations in the immune-microenvironment in recurrent glioblastomas.

Keywords: glioblastoma; lymphocyte; reactive changes; recurrence; tumour microenvironment; tumour‐associated microglia/macrophage.

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References

REFERENCES

    1. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5‐year analysis of the EORTC‐NCIC trial. Lancet Oncol. 2009;10(5):459‐466. doi:10.1016/S1470‐2045(09)70025‐7
    1. Broekman ML, Maas SLN, Abels ER, Mempel TR, Krichevsky AM, Breakefield XO. Multidimensional communication in the microenvirons of glioblastoma. Nat Rev Neurol. 2018;14(8):482‐495. doi:10.1038/s41582‐018‐0025‐8
    1. Morisse MC, Jouannet S, Dominguez‐Villar M, Sanson M, Idbaih A. Interactions between tumor‐associated macrophages and tumor cells in glioblastoma: unraveling promising targeted therapies. Expert Rev Neurother. 2018;18(9):729‐737. doi:10.1080/14737175.2018.1510321
    1. Pires‐Afonso Y, Niclou SP, Michelucci A. Revealing and harnessing tumour‐associated microglia/macrophage heterogeneity in glioblastoma. Int J Mol Sci. 2020;21(3):689. doi:10.3390/ijms21030689
    1. Brandao M, Simon T, Critchley G, Giamas G. Astrocytes, the rising stars of the glioblastoma microenvironment. Glia. 2019;67(5):779‐790. doi:10.1002/glia.23520

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