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Publication : Egr2 and 3 maintain anti-tumour responses of exhausted tumour infiltrating CD8 + T cells.

First Author  Symonds ALJ Year  2023
Journal  Cancer Immunol Immunother Volume  72
Issue  5 Pages  1139-1151
PubMed ID  36342511 Mgi Jnum  J:346621
Mgi Id  MGI:7617185 Doi  10.1007/s00262-022-03319-w
Citation  Symonds ALJ, et al. (2023) Egr2 and 3 maintain anti-tumour responses of exhausted tumour infiltrating CD8 + T cells. Cancer Immunol Immunother 72(5):1139-1151
abstractText  Although T cells can develop into an exhausted state in the tumour microenvironment, tumour infiltrating T cells (TILs) are important to control tumour growth. By analysing single cell RNA-sequencing data from human tumours, we found that the transcription factors Early Growth Response 2 (EGR2) and 3 were highly induced in TILs, but not peripheral CD8 + T cells, in multiple patient cohorts. We found that deficiency of Egr2 and 3 in T cells resulted in enhanced tumour growth and fewer TILs in mouse models. Egr2 is highly expressed together with checkpoint molecules in a proportion of CD8 + TILs and Egr2high cells exhibit better survival and proliferation than Egr2(-/-)Egr3(-/-) and Egr2low TILs. Anti-PD-1 treatment increases Egr2 expression in CD8 + TILs and reduces tumour growth, while anti-PD-1 efficacy is abrogated in the absence of Egr2 and 3. Thus, Egr2 and 3 are important for maintaining anti-tumour responses of exhausted CD8 + TILs.
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