TREM2 mediates MHCII-associated CD4+ T cell response against gliomas

TREM2 介导 MHCII 相关 CD4+ T 细胞对胶质瘤的反应

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作者:Jiaying Zheng, Lingxiao Wang, Shunyi Zhao, Wenjing Zhang, Yuzhou Chang, Aastha Dheer, Shan Gao, Shengze Xu, Katayoun Ayasoufi, Rawan Al-Kharboosh, Manling Xie, Aaron J Johnson, Haidong Dong, Alfredo Quiñones-Hinojosa, Long-Jun Wu

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) was recently highlighted as a novel immune suppressive marker in peripheral tumors. The aim of this study was to characterize TREM2 expression in gliomas and investigate its contribution in glioma progression by using Trem2-/- mouse line. Our results showed that higher TREM2 expression was correlated with poor prognosis in glioma patients. Unexpectedly, TREM2 deficiency did not have a beneficial effect in a pre-clinical model of glioma. The increased TREM2 expression in glioma was likely due to increased myeloid cell infiltration, as evidenced by our single-cell analysis showing that almost all microglia and macrophages in gliomas were TREM2+. Furthermore, we found that deficiency of TREM2 impaired tumor-myeloid phagocytosis and MHCII presentation, and significantly reduced CD4+ T cells in tumor hemispheres. Our results revealed a previously unrecognized protective role of tumor-myeloid TREM2 in promoting MHCII-associated CD4+ T cell response against gliomas.

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