Glial TLR2‐driven innate immune responses and CD8+ T cell activation against brain tumor. Issue 6 (5th February 2019)

• Record Type: Journal Article
• Authors: Chang, Chi Young; Jeon, Sae‐Bom; Yoon, Hee Jung; Choi, Bum‐Kyu; Kim, Sang Soo; Oshima, Masanobu; Park, Eun Jung
• Is Part Of: Glia. Volume 67:Issue 6(2019)
• Page Start: 1179
• Page End: 1195
• Publication Date: 2019-02-05
• Subjects: brain tumor microenvironment -- CD8+ T cells -- glia -- major histocompatibility complex I -- toll‐like receptor 2; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23597
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Growing interest has been focused on the roles of microglia as sentinels and effector cells that guard diverse pathological milieu in the brain. Here, it has been reported that microglial TLR2 is a crucial molecule that confers innate and adaptive immunity against brain tumor. TLR2 is preferentially expressed on microglia, brain‐resident immune cells, in the tumor‐bearing cerebral hemisphere of mouse and rat intracranial tumor models. Microglial TLR2 rapidly responds to brain tumor and modulates the inflammation‐associated immune responses including phagocytosis, which are markedly decreased in TLR2‐deficient mice. We further reveal that TLR2, but not TLR4, is essential for the tumor‐triggered increase of MHC I in microglia. in vitro co‐culture and in vivo experiments show that the glial TLR2‐MHC I axis contributes to the proliferation and activation of CD8 + T cells by brain tumor. In addition, brain tumor‐bearing β2m −/−, Tlr2 −/−, or Rag2 −/− γc −/− mice exhibit higher tumor volumes compared with WT mice with tumor. Survival analysis of GL26‐bearing MHC I‐defective mice also support the contribution of glial TLR2‐MHC I axis to brain tumor immunity. Moreover, using publicly available data sets of human brain tumor patients, we find that glioblastoma (GBM) tissues with high TLR2 level have similar co‐occurrence patterns with MHC I molecules, and the amounts and activity of infiltrating CD8 + T cells are correlated with TLR2 level in tissues from GBM patients. Collectively, our findings provide the importance of glial TLR2‐driven innate and adaptive immune responses in the brain tumor microenvironment. Main Points: Glial TLR2 actively responds to brain tumor and drives inflammatory responses against tumor. TLR2, but not TLR4, is crucial for the tumor‐triggered increase of MHC I in microglia, thereby affecting the activity of CD8 + T cells and tumor growth.