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

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.