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

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-polarized TAMs in glioblastomas and their relationship with CD4TILs, Ibamicroglia, and IDH1 mutation. We also exploreed the prognostic value of these markers on the recurrence-free interval (RFI).

METHODS

The expressions of CD204TAMs, CD4TILs, and Iba1microglia were quantitively assessed in 45 glioblastomas using immunohistochemistry. Kaplan-Meier analysis and Cox hazards were used to examine the relationship between these factors.

RESULTS

CD204TAMs were highly expressed in 32 tumours (71%) and the remaining 13 tumours (29%) had reduced expression. CD4TILs were highly expressed in 10 cases (22%) and 35 cases (77.8%) had low expression. There was an inverse correlation between CD204TAMs and CD4TILs, in which 85% of tumours had a high expression of CD204TAMs and a low expression of CD4TILs. Nevertheless, there was no significant difference in IDH1 mutation status between the two groups (p = 0.779). There was a significant difference in Iba1microglial activation between IDH1 and IDH1 groups (p = 0.031). For cases with a high expression of CD204TAMs and a low expression of CD4TILs, there was a significant difference in RFI after treatment with chemoradiotherapy or radiotherapy (p = 0.030).

CONCLUSION

Glioblastoma with a dense CD204TAMs and few CD4TILs is associated with IDH1. 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.