Poster abstracts
Poster number 114 submitted by Tong Xiao
ZFP148 represses effector differentiation and cytotoxicity of CD8+ T cells during chronic viral infection and cancer
Tong Xiao (Molecular, Cellular, and Developmental Biology Graduate Program), No-joon Song, Payton Weltge (Pelotonia Institute for Immuno-oncology), Yuzhou Chang, Qin Ma (Department of Biomedical Informatics College of Medicine), Jianying Li, Thera H. Pich, Gang Xin (Pelotonia Institute for Immuno-oncology), Juanita L. Merchant (University of Arizona Cancer Center), Zihai Li (Pelotonia Institute for Immuno-oncology)
Abstract:
ZFP148 is one of the Kruppel family of zinc finger transcription factors. It is highly expressed by activated as well as antigen-experienced tumor-infiltrating CD8+ T cells. However, the roles of ZFP148 in regulating CD8+ T cell activation and effector function remain unknown. Here we found that ZFP148 is a negative regulator of CD8+ T cell activation. It is rapidly upregulated upon TCR engagement and requires NFAT- calcineurin signaling. CRISPR-RNP mediated deletion of ZFP148 in TCR transgenic CD8+ T cells enhances their activation and effector molecule production but dampens their anti-tumor capacity after being adoptive transferred into tumor-bearing mice. ZFP148-deleted CD8+ T cells showed significant upregulation of the cell surface receptor Fas (CD95) and display accelerated T cell exhaustion and reduced survival in the tumor microenvironment. Anti-PD1 immune checkpoint blockage therapy shows improved response in CD8+ T cell-specific ZFP148 knockout mice compared with control mice.
Keywords: T cell differention, cancer immunotherapy, transcriptional regulation