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

Zheng, J.; Wang, L.; Zhao, S.; Zhang, W.; Chang, Y.; Dheer, A.; Gao, S.; Xu, S.; Ayasoufi, K.; Al-kharboosh, R.; Xie, M.; Johnson, A. J.; Dong, H.; Wu, L.-J.

doi:10.1101/2023.04.05.535697

bioRxiv · 10.1101/2023.04.05.535697

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

Zheng, J.·Wang, L.·Zhao, S.·Zhang, W.·Chang, Y.·Dheer, A.·Gao, S.·Xu, S.·Ayasoufi, K.·Al-kharboosh, R.·Xie, M.·Johnson, A. J.·Dong, H.·Wu, L.-J.

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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. SUMMARYAuthors found that although higher TREM2 expression is correlated with poor prognosis in glioma patients, its absence has no beneficial effect in a pre-clinical model of glioma. Deficiency of TREM2 impairs myeloid cell phagocytosis of tumor debris, leading to a reduction in MHCII-dependent CD4+ anti-glioma immunity.

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Zheng, J., Wang, L., Zhao, S., Zhang, W., Chang, Y., Dheer, A., Gao, S., Xu, S., Ayasoufi, K., Al-kharboosh, R., Xie, M., Johnson, A. J., Dong, H., Wu, L.-J.. 2023-04-06. TREM2 mediates MHCII-associated CD4+ T cell response against gliomas. https://doi.org/10.1101/2023.04.05.535697

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