The relationship between CD204 M2-polarized tumour-associated macrophages (TAMs), tumour-infiltrating lymphocytes (TILs), and microglial activation in glioblastoma microenvironment: a novel immune checkpoint receptor target

Maher Kurdi; Badrah Alghamdi; Nadeem Shafique Butt; Saleh Baeesa

doi:10.1007/s12672-021-00423-8

The relationship between CD204 ^M2-polarized tumour-associated macrophages (TAMs), tumour-infiltrating lymphocytes (TILs), and microglial activation in glioblastoma microenvironment: a novel immune checkpoint receptor target

Discov Oncol. 2021 Aug 25;12(1):28. doi: 10.1007/s12672-021-00423-8.

Authors

Maher Kurdi^{1

2}, Badrah Alghamdi³, Nadeem Shafique Butt⁴, Saleh Baeesa⁵

Affiliations

¹ Department of Pathology, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia. Ahkurdi@kau.edu.sa.
² Neuromuscular Unit, Centre of Excellence of Genomic Research, King Abdulaziz University, Jeddah, Saudi Arabia. Ahkurdi@kau.edu.sa.
³ Department of Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
⁴ Department of Family and Community Medicine, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Division of Neurosurgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

Background: Tumour associated macrophages (TAMs) and tumour infiltrating lymphocytes (TILs) are considered dominant cells in glioblastoma microenvironment.

Aim: The purpose of this study was to assess the expression of CD204^{+ M2}-polarized TAMs in glioblastomas and their relationship with CD4⁺TILs, Iba⁺microglia, and IDH1 mutation. We also exploreed the prognostic value of these markers on the recurrence-free interval (RFI).

Methods: The expressions of CD204⁺TAMs, CD4⁺TILs, and Iba1⁺microglia were quantitively assessed in 45 glioblastomas using immunohistochemistry. Kaplan-Meier analysis and Cox hazards were used to examine the relationship between these factors.

Results: CD204⁺TAMs were highly expressed in 32 tumours (71%) and the remaining 13 tumours (29%) had reduced expression. CD4⁺TILs were highly expressed in 10 cases (22%) and 35 cases (77.8%) had low expression. There was an inverse correlation between CD204⁺TAMs and CD4⁺TILs, in which 85% of tumours had a high expression of CD204⁺TAMs and a low expression of CD4⁺TILs. Nevertheless, there was no significant difference in IDH1 mutation status between the two groups (p = 0.779). There was a significant difference in Iba1⁺microglial activation between IDH1^mutant and IDH1^wildtype groups (p = 0.031). For cases with a high expression of CD204⁺TAMs and a low expression of CD4⁺TILs, there was a significant difference in RFI after treatment with chemoradiotherapy or radiotherapy (p = 0.030).

Conclusion: Glioblastoma with a dense CD204⁺TAMs and few CD4⁺TILs is associated with IDH1^wildtype. These findings suggest that TAMs masks tumour cell and suppress T-cell tumoricidal functions via immunomodulatory mechanisms. Blockade of the CD204-TAM receptor may prevent this mechanism and allow the evolution of TILs.

Keywords: CD204; Glioblastoma; Immune check point receptors; Microglial activation; Tumour associated macrophages; Tumour infiltrating lymphocytes.